Volume 11 (2014) // Number 5–6 // ISSN 1810-2107
Journal of
2014
Reproductive MedicineNo.5-6
and Endocrinology
– Journal für Reproduktionsmedizin und Endokrinologie –
Andrology Embryology&MolecularBiology Endocrinology Ethics&Law Genetics
GynaecologyContraceptionPsychosomaticMedicineReproductiveMedicineUrology
D·I·R Annual 2013 – German IVF-Registry
V. Blumenauer, U. Czeromin, K. Fiedler, C. Gnoth, L. Happel, J.-S. Krüssel,
M. S. Kupka, A. Tandler-Schneider
Options for Fertility Preservation in Cancer Patients
R. Dittrich et al.
From classical to molecular physiology and back again
N. Einer-Jensen, H. F. R. Hunter
Official Organ: AGRBM, BRZ, DVR, DGA, DGGEF, DGRM, DIR, EFA, OEGRM, SRBM/DGE
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Journal of
Reproductive Medicine and Endocrinology
Publisher
Univ.-Doz. Dr. Dietmar Spitzer
IVF-Zentren Prof. Zech
A-5020 Salzburg, Austria
e-mail: [email protected]
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Embryology and Molecular Biology
Chief Editor
Prof. Dr. med. Hermann M. Behre
Zentrum für Reproduktionsmedizin und
Andrologie
Universitätsklinikum Halle
Martin-Luther-Universität Halle-Wittenberg
Ernst-Grube-Str. 40
D-06120 Halle, Germany
phone +49/345/557-4782
fax +49/345/557-4788
e-mail: [email protected]
Official Organ of the Following
Scientific Societies
Arbeitsgemeinschaft Reproduktionsbiologie des Menschen (AGRBM)
Bundesverband Reproduktionsmedizinischer Zentren Deutschlands (BRZ)
Dachverband Reproduktionsbiologie
und -medizin (DVR)
Deutsche Gesellschaft für Andrologie
(DGA)
Deutsche Gesellschaft für Gynäkologische
Endokrinologie und Fortpflanzungsmedizin (DGGEF)
Deutsche Gesellschaft für Reproduktionsmedizin (DGRM)
Deutsches IVF-Register (D·I·R)
Embryologenforum Austria (EFA)
Österreichische Gesellschaft für Reproduktionsmedizin und Endokrinologie
(OEGRM)
Sektion Reproduktionsbiologie und
-medizin der Deutschen Gesellschaft
für Endokrinologie (SRBM/DGE)
Prof. em. Dr. med. Dr. rer. nat.
Henning M. Beier
Direktor des Instituts für Anatomie und Reproduktionsbiologie a.D.
Institut für Molekulare und Zelluläre Anatomie
RWTH Aachen
D-52057 Aachen, Germany
e-mail: [email protected]
Andrology
Prof. Dr. med. Hans-Christian Schuppe
Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie
Universitätsklinikum Gießen u. Marburg GmbH
D-35392 Gießen, Germany
e-mail:
[email protected]
Prim. Univ.-Prof. Dr. med. Joerg Keckstein
Abteilung für Gynäkologie und Geburtshilfe
Landeskrankenhaus Villach
A-9500 Villach, Austria
e-mail: [email protected]
Prof. Dr. med. Michael Ludwig
Facharzt für frauenheilkunde und Geburtshilfe
Gynäkologische Endokrinologie und Reproduktionsmedizin
amedes
Zentrum für Endokrinologie – Kinderwunsch –
Pränatale Medizin im Barkhof
D-20095 Hamburg, Germany
e-mail: [email protected]
Univ.-Prof. Dr. Gottfried Dohr
Institut für Zellbiologie, Histologie und
Embryologie
Medizinische Universität Graz
A-8010 Graz, Austria
e-mail: [email protected]
Prof. Dr. med. Hans Heinrich van der Ven
Abt. für Gynäkologische Endokrinologie und
Reproduktionsmedizin
Zentrum für Geburtshilfe und Frauenheilkunde
Rheinische Friedrich-Wilhelm-Universität
D-53105 Bonn-Venusberg, Germany
e-mail: [email protected]
Endocrinology
Contraception
Prof. Dr. med. Dr. h. c. mult. Thomas Rabe
Universitäts-Frauenklinik
D-69120 Heidelberg, Germany
e-mail: [email protected]
Prim. Dr. Hans Concin
Abteilung für Frauenheilkunde und Geburtshilfe
Landeskrankenhaus Bregenz
A-6900 Bregenz, Austria
e-mail: [email protected]
Prof. Dr. med. Ludwig Wildt
Klinische Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin
Universitäts-Frauenklinik Innsbruck
A-6020 Innsbruck, Austria
e-mail: [email protected]
Prof. Dr. med. Dr. h. c. mult. Thomas Rabe
Universitäts-Frauenklinik
D-69120 Heidelberg, Germany
e-mail: [email protected]
Ethics and Law
Prof. Dr. med. Heribert Kentenich
Fertility Center Berlin
D-14050 Berlin, Germany
e-mail: [email protected]
Prof. Dr. med. Franz Geisthövel
Centrum für Gynäkologische Endokrinologie
und Reproduktionsmedizin Freiburg (CERF)
D-79098 Freiburg i. Br., Germany
e-mail: [email protected]
Dr. med. Ulrich Hilland
Fertility Center Münsterland
D-46399 Bocholt, Germany
e-mail: [email protected]
Prof. Dr. med. Herbert Zech
Institut für Reproduktionsmedizin und Endokrinologie
A-6900 Bregenz, Austria
e-mail: [email protected]
Editors
Gynaecology
Genetics
Psychosomatic Medicine
PD Dipl.-Psych. Dr. sc. hum. Tewes Wischmann
Universitätsklinikum Heidelberg
D-69115 Heidelberg, Germany
e-mail:
[email protected]
Reproductive Medicine
Dr. Klaus Bühler
Kinderwunsch-Zentrum Ulm & Stuttgart
D-70174 Stuttgart, Germany
e-mail: [email protected]
[email protected]
Prof. Dr. med. Wolfgang Urdl
Universitätsklinik für Frauenheilkunde Graz
A-8010 Graz, Austria
e-mail: [email protected]
Prof. Dr. Dr. med. Wolfgang Würfel
Kinderwunsch Centrum München (KCM)
D-81241 München, Germany
e-mail: [email protected]
CME/DFP
PD Dr. med. Tina Buchholz
Zentrum für Polkörperdiagnostik, Praxis für
Gynäkologie und Genetik, Labor für
Reproduktionsgenetik
D-80538 München, Germany
e-mail: [email protected]
Dipl. Med. Jens W. Jacobeit
Praxis im Chilehaus
Praxis für Andrologie, Endokrinologie und
Transsexualität
D-20095 Hamburg, Germany
e-mail: [email protected]
Univ.-Prof. Mag. Dr. Markus Hengstschläger
Vorstand des Instituts für Medizinische Genetik
Medizinische Universität Wien
A-1090 Wien, Austria
e-mail:
[email protected]
Prof. Dr. med. Sabine Kliesch
Centrum für Reproduktionsmedizin und
Andrologie, Klinische Andrologie
Universitätsklinikum Münster
D-48149 Münster, Germany
e-mail: [email protected]
Urology
See the entire Editorial Board online:
http://www.kup.at/journals/reproduktionsmedizin/editorial.html
234
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Contents
D·I·R
D·I·R Annual 2013 – German IVF-Registry
V. Blumenauer, U. Czeromin, K. Fiedler, C. Gnoth, L. Happel, J.-S. Krüssel, M.S. Kupka,
A. Tandler-Schneider
236
Current Reviews
Options for Fertility Preservation in Cancer Patients
R. Dittrich, L. Lotz, J. Hackl, S. Nichols-Burns, T. Hildebrandt, H. Schneider, I. Hoffmann,
M. W. Beckmann
274
From classical to molecular physiology and back again
N. Einer-Jensen, H. F. R. Hunter
280
CATEGORIES
Mitteilungen der Gesellschaften
286
Medizintechnik
297
Editorial Board
234
Cover Design: Soo-Hee Kim
Cover Pictures:Top down: 1. ICSI. Modified with grateful permission from De Geyter
C, De Geyter M, Behre HM. Assisted reproduction. In: Nieschlag E, Behre HM, Nieschlag S (eds). Andrology – Male Reproductive Health and Dysfunction. 3rd completely revised and updated ed. Springer Verlag GmbH, Heidelberg, 2010; 2. Embryo in
the 8-cell stage. With grateful permission from Lennart Nilsson and Lars Hamberger
(Göteborg). Presentation © H. M. Beier (Aachen); 3. Light microscope demonstration
of human sperms in the ejaculate. With grateful permission from Lennart Nilsson and
Lars Hamberger from the book “Ein Kind entsteht”, Goldmann Verlag, München, and
Albert Bonnier Förlag AB, Stockholm.
Imprint
Official Organ of Following Scientific
Societies:
• Arbeitsgemeinschaft Reproduktionsbiologie
des Menschen (AGRBM) • Bundesverband
Reproduktionsmedizinischer Zentren Deutschlands (BRZ) • Dachverband Reproduktionsbiologie und -medizin (DVR) • Deutsche Gesellschaft für Andrologie (DGA) • Deutsche Gesellschaft für Gynäkologische Endokrinologie
und Fortpflanzungsmedizin (DGGEF)
• Deutsche Gesellschaft für Reproduktionsmedizin (DGRM) • Deutsches IVF-Register
(D·I·R) • Embryologenforum Austria (EFA)
• Österreichische Gesellschaft für Reproduktionsmedizin und Endokrinologie (OEGRM)
• Sektion Reproduktionsbiologie und -medizin
der DeutschenGesellschaft für Endokrinologie
(SRBM/DGE)
Chief Editor:
Prof. Dr. med. Hermann M. Behre
Zentrum für Reproduktionsmedizin und
Andrologie
Universitätsklinikum Halle
Martin-Luther-Universität Halle-Wittenberg
Ernst-Grube-Str. 40, D-06120 Halle, Germany
phone +49/345/557-4782, fax +49/345/557-4788
e-mail: [email protected]
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Krause & Pachernegg GmbH
Verlag für Medizin und Wirtschaft
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Publication:
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Policy: The Journal of Reproductive Medicine and
Endocrinology welcomes submission of clinically
and research oriented reviews in the fields of andrology, embryology, molecular biology, endocrinology,
ethics and law, genetics, gynaecology, contraception,
psychosomatic medicine, urology etc.
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Statements and opinions expressed in articles herein
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in data processing cannot always be avoided. In
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J Reproduktionsmed Endokrinol 2014; 11 (5–6)
235
Contents
Preface
D·I·R Annual 2013 – German IVF-Registry
V. Blumenauer, U. Czeromin, K. Fiedler, C. Gnoth, L. Happel, J.-S. Krüssel, M.S. Kupka, A. Tandler-Schneider
Responsible for this Edition
237
238
Tables
Outcome of ART 2013
239
Registry Participants 1982–2013
239
Total Number of Treatment Cycles 2013
240
Number of Ovum Pick-up Cycles (OPC) 1982–2013
240
Number of Treatments 1982–2013
241
Summary of Statistics in Brief 2013
241
Summary of Statistics in Brief 2012
241
D·I·R Statistics in Brief 2013
242
D·I·R Statistics in Brief 2012
243
Clinical Pregnancies (CP), Miscarriages (MISC), Ectopic Pregnancies (EP), and Still Births (SB) 2012
244
Multiple Births 2012
245
Births as a Function of Number of Embryos Transferred and Age Groups 2000–2012
246
Births as a Function of Number of Embryos Transferred and Treatment Method 2000–2012
247
Fertilisation Rate 2013
248
Distribution of Indications 2013
249
IVF and ICSI – Results 2013
250
TESE and Cryo Transfer – Results 2013
251
Cryo Transfer – Results 2013
251
Outcome (Clinical Pregnancy [CP]) as a Function of Female Age 2013 – IVF
252
Outcome (Clinical Pregnancy [CP]) as a Function of Female Age 2013 – ICSI
253
Clinical Pregnancies (CP)/ET as a Function of the Number of Embryos Transferred and Age Groups 2013
254
Clinical Pregnancies (CP)/Fresh Transfer as a Function of Embryo Quality 2013
255
Clinical Pregnancies (CP)/Frozen Transfer as a Function of Embryo Quality 2013
255
Miscarriage (MISC) Rates as a Function of Female Age and Number of Embryos Transferred 2013
256
Clinical Pregnancy Rate (CPR) as a Function of the Stimulation Protocol 2013
257
Mean Age for Women and Men 1997–2013
258
Duration of Unwanted Childlessness Prior to First Treatment 1997–2013
259
Number of all Treatment Cycles per Woman 1997–2013
259
Children Born 1997–2013 – IVF, ICSI, IVF/ICSI
260
Children Born 1997–2013 – Total (IVF, ICSI, IVF/ICSI, Cryo Transfer)
261
Children as a Function of Week of Gestation (WoG) and Birth Weight (BW) 2012
262
Complications as a Function of Ovum Pick-up (OPU) 2013
264
Ovarian Hyperstimulation Syndrome (OHSS) as a Function of the Stimulation Protocol
265
List of D·I·R Registry Participants 2013
Sponsors
236
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
266
273
Preface
Annual 2013 – The German IVF-Registry
V. Blumenauer, U. Czeromin, K. Fiedler, C. Gnoth, L. Happel, J.-S. Krüssel, M.S. Kupka, A. Tandler-Schneider
It is our great pleasure to present the annual report of the data collected by the
German IVF-Registry. The Registry
looks back onto more than 30 years of
data collection, extraction, and evaluation.
The great advantage of the German IVFRegistry is the electronic data collection
for each initiated treatment cycle since
1996. Meanwhile, more than 1.2 million
ART cycles have been documented in
the database. The prospective documentation as well as the cycle by cycle data
collection are of particular value.
In 2013, 130 of the 131 centers organized in the association “D·I·R” had reported their data to the German IVFRegistry by September 18, 2014.
84,051 cycles have been documented. A
total of 51,242 women were treated in
2013, resulting in a mean of 1.64 cycles
per woman. We are happy to note that
despite the grave changes in reimbursement regulations, the number of treatment cycles has increased steadily again.
Prof. Dr. med. Jan Krüssel
Over all the years, an increase in the
pregnancy rate (PR) has been achieved.
In 2013, the CPR/ET for IVF treatments
was 32.76%; 29.96% after ICSI, and after “Cryo transfer” (frozen-thawed transfer, mostly in the 2-PN stage) 22.19%.
These data demonstrate the high quality
of reproductive medicine in Germany,
arriving at impressive results despite the
restrictive legislation: in accordance with
the “Embryo Protection Act“ of 1990,
the elective single embryo transfer
(eSET) is forbidden in Germany. Egg
donation is prohibited as well. Cryopreservation is allowed but usually only
of 2-PN stage oocytes. Yet the regulation
that only a maximum of three embryos
may be transferred has certainly led to
positive effects. Due to the increasing
quality of stimulation, improved oocyte
treatment, and changes in transfer technology, the number of transferred embryos has decreased by 20% in fresh cycles since 1997. By transferring no more
than an average of 1.87 embryos in fresh
cycles, the doctors for reproductive medicine in Germany have continued to adhere to their responsible approach to-
Dr. med. Ute Czeromin
Chairwoman
wards the reduction of multiples! The
number of twins was cut back from 1,914
in the year 2012 to 1,487 in 2013; the
number of triplets from 61 to 56. This
development certainly is among the
Registry’s many merits and it will continue to vigorously pursue and support
quality assurance of reproductive medicine in Germany.
The results of the comprehensive data
collection in the German IVF-Registry
and its reports have been cited in numerous scientific publications, nationally as
well as internationally, lending support
and impetus to scientific research.
They have furthermore contributed to the
continuous improvement of quality within the German centers for reproductive
medicine. Medical doctors, biologists,
and patients alike have benefited from
the tedious work necessary to collect, export and evaluate as well as publish the
data. Therefore, we express our gratitude
to all involved:
Thank you and keep up the good work!
Dr. med. Andreas Tandler-Schneider
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
237
Responsible for this Edition
Deutsches IVF-Register e. V.
German IVF Registry
Members of the Board
Dr. med. U. Czeromin (Chairwoman 2014)
Prof. Dr. med. J.-S. Krüssel
Dr. med. Andreas Tandler-Schneider
(Member of the Board 2014)
Curators
Dipl.-Biol. V. Blumenauer
Dr. med. K. Fiedler
PD Dr. med. C. Gnoth
Prof. Dr. med. M. Kupka
Dr. med. L. Happel
Past Chairmen
Dr. med. Klaus Bühler (2007–2014)
Prof. Dr. med. R. Felberbaum (1995–2007)
Prof. Dr. med. H.-K. Rjosk (1992–1995)
Prof. Dr. med. F. Lehmann (1982–1992)
D·I·R Office
Monika Uszkoreit · MRU-Consulting GbR
Mommsenstr. 34, 10629 Berlin
Fon +49 30 39 800 743
E-Mail:
[email protected]
Web: www.deutsches-ivf-register.de
D·I·R-Data Management
W&A – Weise & Associates consulting &
technology GmbH
Fon +49 211 522948 - 10
Fax +49 211 522948 - 11
E-Mail [email protected]
Web: www.weise-associates.de
Contact:
Stefan Fitzthum, Manager Customer Care
and Markus Kimmel, Kimmelnet
Mobile: +49 157 383 261 93
E-Mail: [email protected]
Web: www.kimmelnet.de
Design and Layout
a.umi design etc.
Dipl.-Des. Soo-Hee Kim
Fon +49 176 1250 6007
E-Mail: [email protected]
Copyright D·I·R Deutsches IVF-Register® 2014
238
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
Outcome of ART 2013
Centers for IVF-, ICSI-, and Cryo Transfer Treatments
Members of the German IVF-Registry 2013
n = 131
Registry Participants 2013
n = 130
Data Received by Deadline Sep 18 2014
n = 130
Documented Treatment Cycles
n = 84,051
(100.00 %)
Plausible
n = 80,955
(96.32 %)
Prospective (all Cycles)
n = 69,441
(85.78 %)
Prospective (IVF, ICSI, IVF/ICSI)
n = 45,375
(82.63 %)
Number of Women Treated*
n = 51,242
Mean Number of Treatment Cycles per Woman
1.64
Registry Participants 1982 – 2013
IVF-, ICSI- and Cryo Transfer Treatments
1982
1986
1990
[ ... ]
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
IVF
5
28
53
114
118
117
120
118
117
119
121
124
117
128
ICSI
0
0
0
116
120
117
120
118
120
119
124
128
120
129
Cryo
0
0
0
For values from
1991 to 2002 see
www.deutsches-ivfregister.de
101
112
109
109
112
112
117
120
125
119
128
Total
5
28
53
116
120
117
121
118
120
121
124
128
120
129**
*) Base quantity: Total number of women, including implausible treatment cycles
**) 1 Member did not export the 2013 data. Another center had not recorded their cycles for 2013.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
239
D·I·R Annual 2013 – Tables
Total Number of Treatment Cycles 2013
IVF, ICSI, IVF/ICSI, Cryo Transfer – Prospective Data
IVF
ICSI
IVF/ICSI
Cryo Transfer
No Treatment
Total
n
10,053
34,376
946
19,429
4,637
69,441
%
14.48
49.50
1.36
27.98
6.68
100.00
Number of Ovum Pick-up Cycles (OPU) 1982 – 2013
IVF, ICSI* – Prospective and Retrospective Data
IVF
ICSI
55,000
50,000
45,000
40,000
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
13
20
12
20
11
20
10
20
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
19
89
19
88
19
87
19
86
19
85
19
84
19
83
19
82
19
IVF
1982
1986
1990
[ ... ]
742
3,806
7,343
For values from
1991 to 2002 see
www.deutsches-ivfregister.de
ICSI
Total**
742
3,806 7,343
2003
2004
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
2006
2007
2008
2009
2010
2011 2012*** 2013
28,058 11,848 11,410 11,082 11,362 11,264 11,585 11,346 11,341 12,047 12,156
51,389 25,339 26,370 28,015 31,452 34,333 36,712 38,463 40,641 38,897 40,952
80,434 37,633 38,382 39,769 43,612 46,431 49,170 50,798 53,076 51,958 54,237
*) OPUs leading to an IVF- and/or ICSI oocyte treatment
**) In each case, "Total“ also contains values for IVF/ICSI. For 2013 e.g. 1,129 OPUs
***) Starting in 2012, based on registry participants 2012 ff.
240
2005
D·I·R Annual 2013 – Tables
Number of Treatmentà 1982 – 2013
IVF, ICSI, IVF/ICSI, Cryo Transfer – Plausible Data
IVF
1982
1986
1990
[ ... ]
742
3,806
7,343
For values from
1991 to 2002
see www.
deutsches-ivfregister.de
ICSI
IVF/ICSI
Cryo
2004
2005
2006
2007
2008
2009
2010
2011 2012***
2013
28,058 11,848 11,098 11,082 11,362 11,264 11,585 11,346 11,341 12,047 12,156
51,389 25,339 25,532 28,015 31,452 34,333 36,712 38,463 40,641 38,897 40,952
987
446
590
672
798
834
873
989
1,094
1,014
1,129
14,265 16,883 14,471 14,926 16,566 17,646 17,866 17,969 19,228 19,293 20,365
None*
Total**
2003
11,133
742
4,201
8,653
4,928
4,539
4,600
5,137
5,825
5,946
6,289
6,618
6,117
6,353
105,854 59,448 56,232 59,295 65,316 69,902 72,984 75,056 78,922 77,368 80,955
From 1999 on each initiated cycle is documented.
*) No treatment: treatments aborted prior to oocyte culture
**) "Total" may contain GIFT cases. Documentation has been neglected since 2005 due to lack of statistical relevance
***) Starting in 2012, based on registry participants 2012 ff. The total for the year 2010 was corrected
Summary of Statistics in Brief 2013 – CoD Sep 18 2014
IVF, ICSI and IVF/ICSI – Prospective and Retrospective Data
Summary of Statistics in Brief 2012 – CoD Sep 18 2014
IVF, ICSI and IVF/ICSI – Prospective and Retrospective Data
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
241
D·I·R Annual 2013 – Tables
D·I·R Statistics in Brief 2013 – CoD Sep 18 2014
German IVF Registry
242
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
D·I·R Statistics in Brief 2012 – CoD Sep 18 2014
German IVF Registry
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
243
D·I·R Annual 2013 – Tables
Clinical Pregnancies (CP), Miscarriages (MISC), Ectopic
Pregnancies (EP), and Still Births (SB) 2012
Prospective and Retrospective Data
Birth Rate/Transfer for patients with two embryos transferred and a surplus of at least two 2-PN-stage embryos:
IVF 22.04%, ICSI 22.00%, IVF/ICSI 25.36%
IVF
n
ICSI
%
IVF/ICSI
%
n
38,897
n
Cryo Transfer
%
1,014
n
%
Treatment Cycles
12,047
19,293
Clinical Pregnancies
3,280
100.00
10,286
100.00
328
100.00
3,870
100.00
No Information
572
17.44
1,507
14.65
37
11.28
572
14.78
Live Births
2,142
65.30
7,011
68.16
224
68.29
2,439
63.02
Miscarriages
499
15.21
1,620
15.75
60
18.29
791
20.44
Induced Abort. + Fetal Reduc.*
35 (50)
1.07
155 (243)
1.51
6 (7)
1.83
58 (80)
1.50
Ectopic Pregnancies
67
2.04
148
1.44
7
2.13
68
1.76
Children
2,613
Still Births**
18
Malformations
26
Baby-Take-Home-Rate***
8,525
0.55
38
0.79
82
275
0.37
4
0.80
6
2,827
1.22
7
1.83
44
18.02
22.09
12.58
18.67 1
18.751
22.931
12.96 1
20.88 2
20.66 2
24.56 2
14.44 2
**) Number of still births in relation to the number of children born
***) Percentage of births per number of treatments
) Total cycles reduced by the number of cycles with unknown pregnancy outcome
) For cycles with unknown pregnancy outcome, the probable birth rate (births/pregnancy) was calculated and added to the number of known births
2
244
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
1.14
17.78
*) Number of cycles in which an induced abortion was documented. A more detailed differeniation cannot be supplied at this time.
The brackets contain the number of embryos
1
0.18
D·I·R Annual 2013 – Tables
Multiple Births 2012
Prospective and Retrospective Data
%
Singletons
Twins
Triplets
100
90
80
70
30
20
10
0
IVF
ICSI
IVF/ICSI
IVF
CP/ET
n
%
3,280
100.00
Cryo
ICSI
%
n
%
10,286
100.00
IVF/ICSI
%
n
%
328
100.00
Cryo Transfer
%
n
%
3,867
100.00
%
Births
2,142
65.30
100.00
7,011
68.16
100.00
224
68.29
100.00
2,438
63.05
100.00
Singletons
1,685
51.37
78.66
5,543
53.89
79.06
174
53.05
77.68
2,068
53.48
84.82
Twins
443
13.51
20.68
1,422
13.82
20.28
49
14.94
21.88
354
9.15
14.52
Triplets
14
0.43
0.65
46
0.45
0.66
1
0.30
0.45
17
0.44
0.70
Quadruplets
0
0.00
0.00
0
0.00
0.00
0
0.00
0.00
0
0.00
0.00
No Information
572
17.44
1,507
14.65
37
11.28
570
14.74
Miscarriages
499
15.21
1,620
15.75
60
18.29
791
20.46
EPs
67
2.04
148
1.44
7
2.13
68
1.76
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
245
D·I·R Annual 2013 – Tables
Births as a Function of Number of Embryos Transferred
and Age Groups 2000 – 2012*
IVF, ICSI, IVF/ICSI, Cryo Transfer – Prospective and Retrospective Data
Woman´s Age
in Years
Singletons
n
< = 24
25 – 29
30 – 34
35 – 39
> = 40
%
n
Triplets
%
1 Embryo
138
100.00
0
0.00
n
0
Quadruplets
Total
%
n
%
n
0.00
0
0.00
138
2 Embryos
1,617
76.71
482
22.87
9
0.43
0
0.00
2,108
3 Embryos
271
67.75
107
26.75
20
5.00
2
0.50
400
Total
2,026
76.57
589
22.26
29
1.10
2
0.08
2,646
1 Embryo
1,406
95.32
67
4.54
2
0.14
0
0.00
1,475
2 Embryos
15,667
75.62
4,955
23.92
93
0.45
2
0.01
20,717
3 Embryos
2,684
68.71
1,005
25.73
214
5.48
3
0.08
3,906
Total
19,757
75.70
6,027
23.09
309
1.18
5
0.02
26,098
1 Embryo
3,544
96.17
137
3.72
4
0.11
0
0.00
3,685
2 Embryos
32,691
77.49
9,322
22.10
174
0.41
1
0.00
42,188
3 Embryos
7,626
70.83
2,706
25.13
428
3.98
6
0.06
10,766
Total
43,861
77.44
12,165
21.48
606
1.07
7
0.01
56,639
1 Embryo
3,761
96.24
143
3.66
4
0.10
0
0.00
3,908
2 Embryos
24,242
83.11
4,838
16.59
79
0.27
1
0.00
29,160
3 Embryos
10,363
76.72
2,813
20.83
311
2.30
2
0.01
13,489
Total
38,366
82.36
7,794
16.73
394
0.85
3
0.01
46,557
1 Embryo
827
96.27
32
3.73
0
0.00
0
0.00
859
2 Embryos
3,086
90.82
305
8.98
6
0.18
1
0.03
3,398
3 Embryos
2,668
87.02
382
12.46
16
0.52
0
0.00
3,066
Total
6,581
89.87
719
9.82
22
0.30
1
0.01
7,323
Total number of births 2000 – 2012: 139,263
*) Starting in 2012, based on registry participants 2012 ff.
246
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D·I·R Annual 2013 – Tables
Births as a Function of Number of Embryos Transferred and
Treatment Method 2000 – 2012*
Prospective and Retrospective Data
IVF
Singletons
n
%
1 Embryo
2,016
2 Embryos
18,897
3 Embryos
5,966
26,879
76.80
Total
Twins
n
98.53
Triplets
%
n
Quadruplets
Total
%
n
%
0
0.00
0
0.00
2,046
30
1.47
77.98
5,242
21.63
93
0.38
1
0.00
24,233
68.43
2,383
27.33
364
4.17
6
0.07
8,719
7,655
21.87
457
1.31
7
0.02
34,998
ICSI
Singletons
n
Twins
%
n
Triplets
%
n
Quadruplets
%
n
%
Total
1 Embryo
4,201
98.50
64
1.50
0
0.00
0
0.00
4,265
2 Embryos
45,371
79.10
11,791
20.56
197
0.34
3
0.01
57,362
3 Embryos
12,640
74.92
3,723
22.07
502
2.98
6
0.04
16,871
Total
62,212
79.25
15,578
19.85
699
0.89
9
0.01
78,498
Cryo Transfer
Singletons
Twins
Triplets
%
n
n
%
0.00
0
0.00
2,120
56
0.37
0
0.00
15,070
123
2.04
1
0.02
6,035
0.77
1
0.00
23,225
%
1 Embryo
2,068
97.55
2 Embryos
12,991
86.20
2,023
13.42
3 Embryos
4,653
77.10
1,258
20.85
19,712
84.87
3,333
14.35
179
52
2.45
Total
%
n
Total
n
Quadruplets
0
*) Starting in 2012, based on registry participants 2012 ff.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
247
D·I·R Annual 2013 – Tables
Fertilisation Rate 2013
IVF and ICSI – Prospective Data
Embryos per Transfer3 and Children After IVF, ICSI 1997 – 2013
Prospective and retrospective Data
IVF
ICSI
1997
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011*
2012
2013
Embryos Transf.
2.49
2.25
2.19
2.17
2.15
2.11
2.08
2.08
2.06
2.03
2.01
1.99
1.88
1.87
Children/Transf.
0.21
0.24
0.22
0.23
0.23
0.24
0.25
0.25
0.24
0.24
0.22
0.15
0.24
0.18
Children/Deliv.
1.31
1.27
1.26
1.26
1.25
1.23
1.23
1.24
1.24
1.22
1.24
1.26
1.22
1.27
Embryos Transf.
2.56
2.3
2.21
2.17
2.15
2.11
2.09
2.08
2.08
2.06
2.05
2.02
1.91
1.88
Children/Transf.
0.22
0.24
0.22
0.23
0.23
0.24
0.24
0.24
0.23
0.23
0.22
0.15
0.24
0.17
Children/Deliv.
1.29
1.23
1.23
1.23
1.22
1.22
1.20
1.21
1.22
1.21
1.21
1.22
1.22
1.23
CryoEmbryos Transf.
Transfer
Children/Transf.
2.34
2.20
2.14
2.12
2.14
2.10
2.10
2.07
2.07
2.05
2.04
2.02
1.78
1.67
0.10
0.12
0.12
0.12
0.12
0.14
0.14
0.14
0.14
0.14
0.14
0.10
0.15
0.12
Children/Deliv.
1.14
1.16
1.16
1.16
1.17
1.16
1.16
1.16
1.15
1.16
1.16
1.18
1.16
1.17
1) In 507 cases no IVF- or ICSI treatment was performed. 149 are cases in which oocytes were recovered but nevertheless a cryo transfer was performed
2) Reason: e.g. immature oocytes or no sperm available
3) Mean
*) The obvious discrepancy in the figures results from the incomplete data transfer in 2011
248
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
Distribution of Indications 2013
IVF and ICSI – Prospective Data
IVF
Male Factor
Normal
Female Factor
Reduced Semen Quality
n
%
Normal
1,259
Tubal Pathology
Endometriosis
Other**
Total
n
%
n
%
n
%
12.52
721
7.17
828
8.24
2,808
27.93
1,301
12.94
399
3.97
555
5.52
2,255
22.43
573
5.70
198
1.97
331
3.29
1,102
10.96
Hyperandrog./PCO
221
2.20
81
0.81
137
1.36
439
4.37
Ovulatory Dysf.
397
3.95
228
2.27
209
2.08
834
8.30
Psychogen. Factors
4
0.04
1
0.01
3
0.03
8
0.08
Other*
1,096
10.90
274
2.73
822
8.18
2,192
21.80
No Information
17
0.17
10
0.10
388
3.86
415
4.13
3,273
32.56
Total
4,868
48.42
1,912
19.02
10,053
100.00
ICSI
Male Factor
Female Factor
Normal
n
%
Normal
847
2.46
Tubal Pathology
334
0.97
Endometriosis
241
0.70
Hyperandrog./PCO
65
0.19
Reduced Semen Qual.
n
%
9,882
Azoospermia
n
%
28.75
959
2.79
1,418
4.12
39
1,270
3.69
37
952
2.77
57
Other**
n
Total
%
n
%
3,224
9.38
14,912
43.38
0.11
573
1.67
2,364
6.88
0.11
671
1.95
2,219
6.46
0.17
383
1.11
1,457
4.24
Ovulatory Dysf.
157
0.46
1,680
4.89
125
0.36
484
1.41
2,446
7.12
Psychogen. Factors
0
0.00
24
0.07
0
0.00
14
0.04
38
0.11
Other*
503
1.46
4,515
13.13
281
0.82
3,282
9.55
8,581
24.96
No Information
14
0.04
39
0.11
6
0.02
2,300
6.69
2,359
6.86
Total
2,161
6.29
57.54
1,504
4.38
10,931
31.80
34,376
19,780
100.00
*) The indications "sperm antibodies“ and "cervical factor“ are included here
**) The indication "pathological function test“ is included here
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
249
D·I·R Annual 2013 – Tables
IVF and ICSI – Results 2013
Prospective Data
IVF 2013
n
%
Fertilisation %
Embryo %
IVF
10,053
100.00
Successful Fertilis.*
9,337
92.88
100.00
Minimum 1 Embryo
8,920
88.73
95.53
100.00
Transfer %
Clin. Preg. %
ET Performed
8,824
87.77
94.51
98.92
100.00
Clin. Pregnancy
2,950
29.34
31.59
33.07
33.43
Birth
1,318
44.68
100.00
Miscarriage
459
15.56
Ectopic Pregnancy
56
1.90
Not Yet Recorded
1,117
37.86
ICSI 2013 Total
n
Fertilisation %
ICSI
34,376
100.00
Successful Fertilis.*
32,713
95.16
100.00
Minimum 1 Embryo
30,923
89.96
94.53
Embryo %
Transfer %
Clin. Preg. %
100.00
ET Performed
30,710
89.34
93.88
99.31
100.00
Clin. Pregnancy
9,382
27.29
28.68
30.34
30.55
Birth
4,330
46.15
100.00
Miscarriage
1,505
16.04
Ectopic Pregnancy
121
1.29
Not Yet Recorded
3,426
36.52
*) Successful fertilisation of at least one oocyte per cycle
250
%
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
TESE and Cryo Transfer – Results 2013
Prospective Data
ICSI/TESE 2013
n
%
Fertilisation %
ICSI
1,996
100.00
Successful Fertilis.*
1,824
91.38
100.00
Minimum 1 Embryo
1,799
90.13
98.63
Embryo %
Transfer %
Clin. Preg. %
100.00
ET Performed
1,702
85.27
93.31
94.61
100.00
Clin. Pregnancy
462
23.15
25.33
25.68
27.14
100.00
Birth
206
44.59
Miscarriage
66
14.29
Ectopic Pregnancy
8
1.73
Not Yet Recorded
182
39.39
Cryo Transfer – Results 2013
Prospective Data
Cryo Transfer 2013
n
%
Cryo Transfer Cycles
19,429
100.00
PN %
Transfer %
Clin. Preg. %
Thawed PN
17,982
92.55
100.00
ET Performed
17,719
91.20
98.54
100.00
Clin. Pregnancy
3,999
20.58
22.24
22.57
Birth
1,817
45.44
Miscarriage
721
18.03
100.00
Ectopic Pregnancy
68
1.70
Not Yet Recorded
1,393
34.83
*) Successful fertilisation of at least one oocyte per cycle
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
251
D·I·R Annual 2013 – Tables
Outcome (Clinical Pregnancy (CP)) as a Function of
Female Age 2013
Prospective Data
IVF 2013
%
Clin. Preg./ET
Miscarriages/Clin. Preg.
%
50
100
45
90
40
80
35
70
30
60
25
50
20
40
15
30
10
20
5
10
0
0
n
<=24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
>=44 Years
42
68
140
187
229
286
421
481
513
587
591
656
677
683
669
747
735
389
265
199
259
ET
% 33.33 48.53 41.43 40.64 44.98 40.56 38.24 39.71 42.69 41.91 40.10 38.41 35.16 32.94 29.45 27.58 26.12 21.85 18.49 13.57 9.65 CP/ET
Oocytes1
Insemin.1
1,092
11.94
11.70
30 – 34
2,932
10.52
35 – 39
3,856
8.49
Age in
Years
< = 29
OPU
ET/OPU
%
Trans.
Embr.1
CP
CP/OPU
%
CP/ET
%
CP/ET: 2 Embr. transf.
+ min. 2 2-PN surplus
952
87.18
1.86
400
36.63
42.02
44.35
10.35
2,593
88.44
1.88
1,054
35.95
40.65
43.10
8.34
3,432
89.00
1.90
1,118
28.99
32.58
35.61
40
853
7.01
6.85
735
86.17
1.99
192
22.51
26.12
29.31
41
472
6.28
6.14
389
82.42
1.93
85
18.01
21.85
25.70
42
295
6.01
5.92
265
89.83
1.94
49
16.61
18.49
22.99
43
242
5.83
5.74
199
82.23
2.06
27
11.16
13.57
16.46
44
184
5.11
5.00
149
80.98
1.91
13
7.07
8.72
12.24
45
80
6.63
6.43
73
91.25
2.00
8
10.00
10.96
12.73
>=46
47
3.74
3.60
37
78.72
1.73
4
8.51
10.81
20.00
10,053
8.99
8.83
8,824
87.77
1.90
2,950
29.34
33.43
36.72
Gesamt
1) Mean
252
ET
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
Outcome (Clinical Pregnancy (CP)) as a Function of
Female Age 2013
Prospective Data
ICSI 2013
%
Clin. Preg./ET
Miscarriages/Clin. Preg.
%
50
100
45
90
40
80
35
70
30
60
25
50
20
40
15
30
10
20
5
10
0
0
n
<=24
25
26
27
28
191
248
477
609
873
29
30
31
32
33
34
35
36
37
38
39
40
41
42
1,102 1,412 1,759 2,001 2,210 2,204 2,320 2,348 2,322 2,060 2,292 2,255 1,343 1,092
43
719
>=44 Years
873
ET
% 41.36 37.90 40.88 39.24 39.52 41.02 38.60 36.38 36.43 37.96 33.94 32.80 32.58 30.32 28.40 25.70 22.48 18.09 15.75 12.80 6.76 CP/ET
Oocytes1
Insemin.1
Age in
Years
OPU
< = 29
3,859
12.44
9.75
30 – 34
10,506
11.15
8.82
35 – 39
12,594
9.06
7.22
2,530
7.51
6.06
40
ET
ET/OPU
%
Trans.
Embr.1
CP
CP/OPU
%
CP/ET
%
CP/ET: 2 Embr. transf.
+ min. 2 2-PN surplus
3,500
90.70
1.89
1,404
36.38
40.11
42.25
9,586
91.24
1.89
3,501
33.32
36.52
38.43
11,342
90.06
1.90
3,404
27.03
30.01
33.12
2,255
89.13
1.94
507
20.04
22.48
26.05
41
1,521
6.70
5.37
1,343
88.30
1.92
243
15.98
18.09
21.10
42
1,271
6.25
5.02
1,092
85.92
1.93
172
13.53
15.75
18.44
43
899
5.79
4.73
719
79.98
1.89
92
10.23
12.80
14.99
44
552
5.36
4.38
462
83.70
1.82
45
8.15
9.74
13.41
45
309
4.67
3.84
250
80.91
1.85
13
4.21
5.20
7.95
>=46
231
3.77
3.14
161
69.70
1.58
1
0.43
0.62
1.37
34,272
9.54
7.58
89.61
1.89
9,382
27.38
30.55
Gesamt
30,710
33.73
1) Mean
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
253
D·I·R Annual 2013 – Tables
Clinical Pregnancies (CP)/ET as a Function of the Number
of Embryos Transferred and Age Groups 2013
IVF, ICSI, Cryo Transfer – Prospective Data
IVF
1 Embryo
Age in Years
ET
< = 24
2 Embryos
CP/ET %
3
66.67
ET
3 Embryos
CP/ET %
35
34.29
ET
Total
CP/ET %
2
0.00
ET
CP/ET %
40
33.33
25 – 29
107
23.36
803
45.29
25
32.00
935
42.42
30 – 34
327
25.08
2,133
43.06
129
43.41
2,589
40.65
35 – 39
580
18.62
2,446
36.06
379
32.45
3,405
32.58
40 – 44
383
9.40
945
24.13
420
26.27
1,748
21.07
> = 45
32
0.00
47
17.02
28
10.71
107
10.91
Total
1,432
17.67
6,409
37.66
983
30.57
8,824
33.43
ICSI
1 Embryo
Age in Years
< = 24
ET
2 Embryos
CP/ET %
22
ET
3 Embryos
CP/ET %
22.73
150
44.67
ET
Total
CP/ET %
ET
CP/ET %
12
50.00
184
41.36
25 – 29
383
27.94
2,746
42.33
194
38.66
3,323
40.04
30 – 34
1,284
25.20
7,627
38.79
667
34.33
9,578
36.52
35 – 39
2,063
17.29
7,817
33.74
1,476
29.66
11,356
30.01
40 – 44
1,549
9.21
3,004
21.07
1,316
22.10
5,869
18.04
> = 45
176
0.57
132
4.55
92
7.61
400
3.41
Total
5,477
17.08
21,476
34.76
3,757
27.82
30,710
30.55
Cryo Transfer
1 Embryo
Age in Years
< = 24
254
ET
2 Embryos
CP/ET %
11
0.00
ET
90
3 Embryos
CP/ET %
25.56
ET
12
Total
CP/ET %
25.00
ET
CP/ET %
113
24.22
25 – 29
271
11.55
1,192
29.78
298
26.36
1,761
26.68
30 – 34
982
17.78
4,173
26.30
1,354
28.68
6,509
25.32
35 – 39
1,289
15.16
4,283
23.19
1,386
25.79
6,958
22.18
40 – 44
525
10.10
1,280
14.30
448
18.30
2,253
15.20
> = 45
32
6.25
60
3.33
33
6.06
125
4.58
Total
3,110
14.70
23.88
3,531
24.89
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
11,078
17,719
22.57
D·I·R Annual 2013 – Tables
Clinical Pregnancies (CP)/Fresh Transfer as a Function
of Embryo Quality 2013
IVF, ICSI, IVF/ICSI – Prospective Data
Quality
Ideal
< = 29 Years
Not Ideal
ET
CP/ET %
30 – 34 Years
ET
35 – 39 Years
CP/ET %
ET
CP/ET %
> = 40 Years
ET
Total
CP/ET %
ET
CP/ET %
0
1
79
11.39
272
12.87
484
7.23
545
10.28
1,380
9.78
0
2
258
24.03
813
21.65
885
17.29
350
8.57
2,306
18.26
0
3
20
20.00
67
11.94
117
22.22
92
10.87
296
16.22
1
0
491
31.16
1,465
29.49
2,532
17.14
1,553
12.49
6,041
20.08
1
1
443
34.54
1,236
33.25
1,364
21.77
657
18.72
3,700
26.59
1
2
31
32.26
82
24.39
126
25.40
197
19.80
436
23.17
2
0
3,042
45.38
7,849
42.64
8,057
37.35
3,064
23.20
22,011
38.38
2
1
31
41.94
123
33.33
294
28.23
291
16.49
739
25.03
3
0
157
41.40
574
39.72
1,346
31.72
1,351
24.13
3,428
30.51
4,552
40.63
37.84
15,205
29.57
8,100
18.98
40,337
31.32
Total
12,481
Clinical Pregnancies (CP)/Frozen Transfer as a Function
of Embryo Quality 2013
Cryo Transfer – Prospective Data
Quality
IVF
Ideal
Not Ideal
0
1
177
7.91
576
10.42
0
2
340
10.00
1,106
13.83
0
3
66
7.58
222
12.16
1
0
602
18.77
2,093
18.16
1
1
482
18.88
1,501
22.45
1
2
83
25.30
236
21.19
2
0
1,651
25.86
5,850
26.62
2
1
110
30.00
668
27.25
3
0
321
29.28
942
26.54
3,832
21.71
Total*
ET
ICSI
CP/ET %
ET
13,194
CP/ET %
22.71
*) In 84 cases the preceding treatment was IVF / ICSI; in 609 cases the preceding treatment is unknown.
From these 693 cases, an additional 171 pregnancies resulted.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
255
D·I·R Annual 2013 – Tables
Miscarriage (MISC) Rates as a Function of Female Age
and Number of Embryos Transferred 2013
Prospective Data
IVF, ICSI, IVF/ICSI
1 Embryo
Age in Years
CP
< = 24
2 Embryos
MISC/CP %
8
37.50
CP
MISC/CP %
79
10.13
3 Embryos
CP
Total
MISC/CP %
6
0.00
CP
MISC/CP %
93
11.83
25 – 29
140
13.57
1,504
10.04
83
14.46
1,727
10.54
30 – 34
425
13.65
3,999
12.55
285
16.14
4,709
12.87
35 – 39
485
17.73
3,622
16.54
546
17.77
4,653
16.81
40 – 44
190
33.16
836
27.15
400
34.50
1,426
30.01
> = 45
1
0.00
14
21.43
10
80.00
25
44.00
Total
1,249
18.33
10,054
14.82
1,330
22.63
12,633
15.99
Cryo Transfer
1 Embryo
Age in Years
256
CP
2 Embryos
MISC/CP %
CP
MISC/CP %
3 Embryos
CP
Total
MISC/CP %
CP
MISC/CP %
< = 24
0
0.00
23
21.74
3
0.00
26
19.23
25 – 29
29
17.24
455
17.36
58
10.34
542
16.61
30 – 34
222
15.77
1,066
17.73
238
18.07
1,526
17.50
35 – 39
241
24.07
969
15.38
271
21.40
1,481
17.89
40 – 44
102
14.71
183
24.04
133
25.56
418
22.25
> = 45
2
0.00
2
50.00
2
0.00
6
16.67
Total
596
18.96
2,698
17.31
705
20.00
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
3,999
18.03
D·I·R Annual 2013 – Tables
Clinical Pregnancy Rate (CPR) as a Function of
the Stimulation Protocol 2013
Prospective Data
IVF
u-FSH
rec-FSH
hMG
recLH u. recFSH recLH u. hMG
Other*
No Info.
Total
Short GnRHa
3
226
302
32
103
1
2
669
Transfer Rate (%)
100.00
93.78
91.24
91.43
91.96
100.00
100.00
91.77
CP/ET (%)
66.67
28.76
32.12
43.75
20.39
0.00
0.00
29.75
88
1,218
537
175
361
19
4
2,402
Transfer Rate (%)
89.80
88.58
92.91
89.29
93.04
61.29
100.00
89.96
CP/ET (%)
37.50
39.49
33.15
34.29
34.63
36.84
25.00
36.84
20
245
203
64
132
14
161
839
Long GnRHa
No GnRHa-Analoga
Transfer Rate (%)
86.96
92.11
90.63
98.46
84.08
93.33
72.20
86.23
CP/ET (%)
45.00
35.10
34.48
29.69
34.09
28.57
19.88
31.59
GnRHa-Antagonists
83
2,790
923
517
495
88
18
4,914
Transfer Rate (%)
93.26
86.86
86.97
84.20
86.54
83.81
60.00
86.46
CP/ET (%)
38.55
34.91
28.88
26.89
31.92
31.82
22.22
32.59
194
4,479
1,965
788
1,091
122
185
8,824
u-FSH
rec-FSH
hMG
Other*
No Info.
Total
Total
ICSI
recLH u. recFSH recLH u. hMG
Short GnRHa
27
727
733
87
336
63
21
1,994
Transfer Rate (%)
84.38
90.65
91.51
90.63
98.82
53.39
0.00
90.51
CP/ET (%)
18.52
24.48
23.87
24.14
14.88
17.46
0.00
22.52
139
4,446
1,702
691
1,646
139
21
8,784
Transfer Rate (%)
94.56
93.72
93.16
90.45
91.70
89.68
80.77
92.87
CP/ET (%)
39.57
35.70
31.37
31.69
33.05
30.94
38.10
34.04
38
870
572
147
563
38
624
2,852
Long GnRHa
No GnRHa-Analoga
Transfer Rate (%)
88.37
89.60
86.14
84.48
83.28
97.44
0.00
83.81
CP/ET (%)
39.47
33.22
31.29
30.61
27.00
42.11
0.00
28.37
GnRHa-Antagonists
148
9,323
2,951
1,957
2,278
325
98
17,080
Transfer Rate (%)
90.24
89.92
89.78
85.76
83.69
89.04
79.03
88.44
CP/ET (%)
26.35
32.97
24.03
29.94
27.88
0.00
16.33
29.62
352
15,366
5,958
2,882
4,823
565
764
30,710
Total
*) e.g. u-FSH and hMG, Clomifen/rec-FSH, Clominfen/hMG etc.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
257
D·I·R Annual 2013 – Tables
Mean Age for Women and Men 1997 – 2013*
IVF, ICSI, IVF/ICSI – Prospective and Retrospective Data
n = 757,532 Treatment Cycles with Plausible Age Documentation
Age in Years
40.0
38.6
Man
38.4
Woman
38.2
Mean
Man
2013: 38.64
38.0
95% Confidence Interval
(CI) (e.g. with a probability of
95 %, the mean women´s age
is between 32.51 and 32.65
years in 1997)
37.8
37.6
37.4
37.2
37.0
36.8
36.6
36.4
36.2
36.0
35.8
35.6
35.4
35.2
35.0
34.8
Woman
2013: 35.20
34.6
34.4
34.2
34.0
33.8
33.6
33.4
33.2
33.0
32.8
32.6
32.4
32.2
32.0
13
20
12
20
11
20
10
20
09
20
08
20
07
20
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
06
20
4
258
05
20
0
20
03
20
02
20
0
01
20
0
20
99
19
98
19
97
19
*) Starting in 2012, based on registry participants 2012 ff.
Year
D·I·R Annual 2013 – Tables
Duration of Unwanted Childlessness Prior to First
Treatment 1997 – 2013*
IVF, ICSI, IVF/ICSI – Prospective and Retrospective Data
n = 374,725 First Treatments with Known
Duration of Unwanted Childlessness
Duration of Unwanted Childlessness Prior to First Treatment in Years
5.5
5.4
5.3
5.2
5.1
5.0
4.9
4.8
4.7
4.6
4.5
4.4
4.3
4.2
4.1
4.0
3.9
3.8
3.7
3.6
3.5
3.4
3.3
3.2
3.1
3.0
13
20
12
20
11
20
10
20
09
20
08
20
07
20
06
20
4
05
20
0
20
03
20
02
20
0
01
20
0
20
99
19
98
19
97
19
Year
*) Starting in 2012, based on registry participants 2012 ff.
Number of all Treatment Cycles per Woman 1997 – 2013*
IVF, ICSI, IVF/ET, Cryo ET – Prospective and Retrospective Data, Regardless of the Result
n
Treatments per Woman
n = 477,252 Women
10
9
8
7
6
5
4
3
2
1
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
40
42
%
[Proportion of Women
with n Treatments]
*) Starting in 2012, based on registry participants 2012 ff.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
259
D·I·R Annual 2013 – Tables
Children Born 1997 – 2013**
Prospective and Retrospective Data
IVF, ICSI, IVF/ICSI
Singletons
Twins
Triplets
Quadruplets
Total
n
%
n
%
n
%
n
%
n
2001
*
6,798
(6,774)
60.89
(61.04)
3,956
(3,919)
35.43
(35.31)
411
(405)
3.68
(3.65)
0
(0)
-
11,165
(11,098)
2002
*
7,746
(7,724)
62.59
(62.78)
4,256
(4,210)
34.39
(34.22)
366
(362)
2.96
(2.94)
8
(7)
0.06
(0.06)
12,376
(12,303)
2003
*
10,723
(10,688)
62.13
(62.78)
5,960
(5,866)
34.53
(34.22)
552
(533)
3.20
(2.94)
24
(24)
0.14
(0.14)
17,259
(17,111)
2004
*
5,368
(5,352)
63.69
(62.46)
2,826
(2,801)
33.53
(34.28)
234
(223)
2.78
(3.11)
0
(0)
-
8,428
(8,376)
2005
*
5,527
(5,515)
63.84
(63.90)
2,936
(2,906)
33.91
(33.44)
183
(179)
2.11
(2.66)
12
(11)
0.14
(0.13)
8,658
(8,611)
2006
*
5,906
(5,894)
65.50
(64.05)
2,922
(2,890)
32.41
(33.75)
189
(174)
2.10
(2.08)
0
(0)
-
9,017
(8,958)
2007
*
6,663
(6,628)
65.45
(64.69)
3,504
(3,471)
33.9.
(33.88)
150
(143)
1.45
(1.40)
4
(4)
0.04
(0.04)
10,231
(10,246)
2008
*
6,696
(6,672)
64.09
(64.34)
3,528
(3,481)
33.77
(33.57)
216
(209)
2.07
(2.02)
8
(8)
0.08
(0.08)
10,448
(10,370)
2009
*
7,253
(7,217)
65.89
(66.02)
3,560
(3,523)
32.34
(32.23)
186
(183)
1.69
(1.67)
8
(8)
0.07
(0.07)
11,007
(10,931)
2010
*
6,767
(6,724)
64.42
(64.62)
3,554
(3,507)
33.83
(33.70)
183
(175)
1.74
(1.68)
0
(0)
-
10,504
(10,406)
2011
*
6,940
(6,880)
63.64
(63.95)
3,856
(3,832)
35.00
(35.06)
219
(216)
1.98
(1.97)
0
(0)
-
11,015
(10,928)
2012
*
7,424
(7,402)
64.53
(64.86)
3,892
(3,828)
33.83
(33.54)
189
(183)
1.64
(1.60)
0
(0)
-
11,505
(11,413)
2013
*
5,127
(5,112)
61.45
(61.93)
3,030
(2,974)
36.32
(36.03)
186
(168)
2.23
(2.04)
0
(0)
-
8,343
(8,254)
*) The values in brackets indicate live births. Totalling 1997 – 2013:
107,134 (103,697) singletons, 58,533 (57,814) twins, 5,497 (5,223) triplets, 88 (85) quadruplets. In total: 171,252 (166,819)
**) Starting in 2012, based on registry participants 2012 ff.
260
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
Children Born 1997 – 2013**
Prospective and Retrospective Data
Total (IVF, ICSI, IVF/ICSI, Cryo Transfer)
Singletons
Twins
Triplets
Quadruplets
Total
n
%
n
%
n
%
n
%
n
2001
*
7,795
(7,764)
62.20
(62.33)
4,288
(4,248)
34.21
(34.10)
450
(444)
3.59
(3.56)
0
(0)
-
12,533
(12,456)
2002
*
8,930
(8,902)
63.84
(64.02)
4,662
(4,615)
33.33
(33.19)
387
(382)
2.77
(2.75)
8
(7)
0.06
(0.05)
13,987
(13,906)
2003
*
11,922
(11,887)
63.16
(63.48)
6,334
(6,237)
33.55
(33.31)
597
(578)
3.16
(3.09)
24
(24)
0.13
(0.13)
18,877
(18,726)
2004
*
6,891
(6,869)
65.63
(65.81)
3,336
(3,306)
31.77
(31.68)
273
(262)
2.6
(2.51)
0
(0)
-
10,500
(10,437)
2005
*
7,038
(7,020)
65.76
(65.93)
3,440
(3,408)
32.14
(32.01)
213
(209)
1.99
(1.96)
12
(11)
0.11
(0.10)
10,703
(10,648)
2006
*
7,419
(7,402)
66.87
(67.14)
3,450
(3,417)
31.10
(30.99)
222
(202)
2.00
(1.83)
4
(4)
0.04
(0.04)
11,095
(11,025)
2007
*
8,407
(8,364)
66.35
(66.45)
4,976
(4,043)
32.17
(32.12)
183
(176)
1.44
(1.40)
4
(4)
0.03
(0.03)
12,670
(12,587)
2008
*
8,444
(8,416)
65.79
(66.07)
4,142
(4,084)
32.27
(32.06)
240
(230)
1.87
(1.81)
8
(8)
0.06
(0.06)
12,834
(12,738)
2009
*
9,016
(8,969)
67.32
(67.42)
4,152
(4,114)
31.00
(30.92)
216
(213)
1.61
(1.60)
8
(8)
0.06
(0.06)
13,392
(13,304)
2010
*
8,619
(8,566)
66.18
(66.35)
4,156
(4,105)
31.91
(31.80)
249
(239)
1.91
(1.85)
0
(0)
-
13,024
(12,910)
2011
*
8,839
(8,767)
64.55
(64.03)
4,556
(4,526)
33.27
(33.05)
298
(294)
2.18
(2.15)
0
(0)
-
13,693
(13,587)
2012
*
9,498
(9,470)
66.23
(66.50)
4,602
(4,536)
32.09
(31.85)
240
(234)
1.67
(1.64)
0
(0)
-
14,340
(14,240)
2013
*
6,744
(6,724)
63.50
(63.95)
3,652
(3,584)
34.38
(34.08)
225
(207)
2.12
(1.97)
0
(0)
-
10,621
(10,515)
*) The values in brackets indicate live births. Totalling 1997 – 2013:
129,947 (129,810) singletons, 66,326 (65,558) twins, 6,016 (5,828) triplets, 92 (89) quadruplets. In total: 202,381 (201,285)
**) Starting in 2012, based on registry participants 2012 ff.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
261
D·I·R Annual 2013 – Tables
Children as a Function of Week of Gestation (WoG)
and Birth Weight (BW) 2012*
Singletons 2012
WoG
n
< 25
25
26
27
28
29
30
31
32
33
34
35
36
23
7
7
16
18
23
24
33
53
98
158
226
436 1,088 1,924 2,280 1,886 380
950
37
38
39
40
41
> 41
Total
43
8,723
BW Q 25
450
620
800
830
BW Median
550
670
890
925
1,130 1,200 1,450 1,480 1,980 2,200 2,375 2,550 2,840 3,020 3,130 3,270 3,390 3,220 2,980
BW Q 75
650
790
980 1,100 1,320 1,560 1,770 1,920 2,170 2,390 2,680 2,920 3,110 3,420 3,590 3,710 3,860 3,960 3,870 3,660
1,048 1,324 1,492 1,650 1,800 2,167 2,460 2,600 2,835 3,110 3,300 3,410 3,570 3,650 3,400 3,320
Percentiles 2012: p25 = 38th WoG, p50 = 39th WoG, p75 = 40th WoG;
Percentiles 1997–2012: p25 = 38th WoG, p50 = 39th WoG, p75 = 40th WoG
Proportion of children born before the completion of the 37th WoG: 25.34%
Twins 2012
WoG
n
< 25
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
Total**
50
24
20
38
48
72
78
114
192
314
392
540
908
916
277
77
10
4,071
905
960
BW Q 25
505
740
830
1,190 1,350 1,490 1,700 1,830 1,990 2,180 2,380 2,510 2,580 2,460 2,840
2,020
BW Median
578
808
927
1,050 1,200 1,365 1,480 1,700 1,880 1,980 2,235 2,400 2,600 2,743 2,800 2,820 2,940
2,430
BW Q 75
700
890
963
1,150 1,320 1,490 1,650 1,820 2,085 2,160 2,420 2,640 2,810 2,980 3,060 3,290 3,000
2,760
Percentiles 2012: p25 = 34th WoG, p50 = 36th WoG, p75 =37th WoG;
Percentiles 1997–2012: p25 = 34th WoG, p50 = 36th WoG, p75 = 37th WoG
Proportion of children born before the completion of the 37th WoG: 91.03%
**) The total contains 1 case with a WoG > 40
Triplets 2012
WoG
n
24
25
26
27
28
29
30
31
32
33
34
35
Total***
0
3
0
15
3
21
24
39
42
48
6
9
210
BW Q 25
-
810
-
840
905
1,100
1,240
1,350
1,490
1,770
1,760
2,110
1,340
BW Median
-
850
-
960
1,170
1,440
1,405
1,554
1,730
1,945
1,855
2,430
1,655
BW Q 75
-
860
-
1,025
1,210
1,575
1,590
1,800
1,800
2,150
1,900
2,880
1,900
Percentiles 2012: p25 = 31st WoG, p50 = 32nd WoG, p75 =34th WoG;
Percentiles 1997–2012: p25 = 30th WoG, p50 = 32nd WoG, p75 = 33th WoG
Proportion of children born before the completion of the 37th WoG: 100.00%
***) The total does not contain a single case of birth weight at gestational week > 35
*) Children with plausible birth weight and week of gestation, using prospective and retrospective data
262
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
D·I·R Annual 2013 – Tables
Children as a Function of Week of Gestation (WoG)
and Birth Weight (BW) 2012*
Singletons 2012
n
2,400
2,200
2,100
2,000
1,900
1,800
1,700
1,600
1,500
g
4,000
3,750
3,500
3,250
3,000
2,750
2,500
2,250
2,000
1,750
1,500
1,250
1,000
750
500
250
0
BW
25th , 50th, 75th Percentile WoG
1,400
1,300
1,200
1,100
1,000
900
800
700
600
500
400
300
200
100
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
0
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
Twins 2012
g
BW
25th , 50th, 75th Percentile WoG
3,500
3,250
3,000
2,750
2,500
2,250
2,000
1,750
1,500
1,250
1,000
750
500
250
0
n
900
800
700
600
500
400
300
200
100
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
0
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
Triplets 2012
g
3,000
2,750
2,500
2,250
2,000
1,750
1,500
1,250
1,000
750
500
250
0
BW
25th , 50th, 75th Percentile WoG
n
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
<25 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 >41 WoG
*) Children with plausible birth weight and week of gestation, using prospective and retrospective data
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
263
D·I·R Annual 2013 – Tables
Complications as a Function of Ovum Pick-up (OPU) 2013
Prospective Data
Total OPU´s
46,898
100.00%
No Information
1
0.00%
No Complications
46,477
99.10%
Complications
420
0.90%
Complications
n
%
Vaginal Bleeding
234
55.71
Intraabdom. Bleeding
104
24.76
Intestinal Tract Injury
2
0.48
Peritonitis
1
0.24
Hospitalisation
21
5.00
Surgery
35
8.33
Other
23
5.48
Total
264
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
420
100.00
D·I·R Annual 2013 – Tables
Ovarian Hyperstimulation Syndrome (OHSS) as
a Function of the Stimulation Protocol
IVF, ICSI, IVF/ICSI – Prospective Data
Stimulation
%
Oocytes Retrieved
OHSS III
OHSS III/Stim %
Short GnRH
3,272
6.64
7.05
1
0.03
FSH only
1,181
8.17
1
0.03
hMG only
1,291
6.62
0
-
FSH + hMG
642
6.21
0
-
Other
150
5.79
0
-
No Information
8
3.50
0
-
Long GnRH
12,954
10.23
50
0.39
FSH only
6,746
11.34
23
0.18
26.27
hMG only
2,638
8.54
3
0.02
FSH + hMG
2,444
9.55
23
0.18
Other
1,105
9.00
0
-
No Information
21
7.71
1
0.01
No Analoga
5,764
5.48
3
0.05
FSH only
2,192
6.22
1
0.02
hMG only
1,480
4.70
1
0.02
FSH + hMG
28
5.93
1
0.02
Other
1,409
7.33
0
-
No Information
655
0.80
0
-
GnRH-Antagonists
27,317
8.86
71
0.26
FSH only
15,003
10.30
50
0.18
11.69
55.40
hMG only
5,088
5.82
2
0.01
FSH + hMG
3,690
7.73
12
0.04
Other
3,409
8.47
7
0.03
No Information
127
3.73
0
-
Total
49,307
8.70
125
0.25
100.00
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
265
Registry Participants 2013
Kinderwunschzentrum Dresden
Praxisklinik Dr. med. H.-J. Held
Dr. med. Hans-Jürgen Held
Prager Straße 8a
01069 Dresden
T: 0351-50100-0, F: 0351-501400-28
[email protected]
www.ivf-dresden.de
Gynäkologische Endokrinologie und Reproduktionsmedizin der Universitätsfrauenklinik
Dresden
Dr. med. Maren Goeckenjan, Prof. Dr. med.
Henry Alexander, Constanze Reisenbüchler,
Dr. rer. nat. Gudrun Keck
Fetscherstraße 74
01307 Dresden
T: 0351-4583491, F: 0351-4585351
[email protected]
www.uniklinikum-dresden.de/gyn
Kinderwunschzentrum Leipzig-Chemnitz
Dr. med. Fayez Abu Hmeidan, Dr. med. Petra
Jogschies, Dörte Geistert, Laila Shugair
Goldschmidtstraße 30
04103 Leipzig
T: 0341-141200, F: 0341-1412081
[email protected]
www.ivf-leipzig.de
Kinderwunschzentrum Praxisklinik City
Leipzig
Dr. med. Astrid Gabert, Dr. med. Katharina
Bauer, Dr. med. Isabel Schwandt, Jana Sonneck,
Dr. med. Doreen Marx, Prof. Dr. med. Henry
Alexander, Dr. rer. nat. Stefanie Breuer
Petersstraße 1
04109 Leipzig
T: 0341-215855-0, F: 0341-215855-17
[email protected]
www.ivf-city-leipzig.de
Universitätsklinikum Halle (Saale)
Zentrum für Reproduktionsmedizin und
Andrologie
Univ.-Prof. Dr. med. Hermann M. Behre,
Dr. med. Petra Kaltwaßer, Dr. med. Solveig
Köller, Dr. rer. nat. Ewald Seliger,
Dr. rer. nat. Thomas Greither
Ernst-Grube-Straße 40
06120 Halle (Saale)
T: 0345-557-3332, F: 0345-557-4788
[email protected]
www.kinderwunsch-halle.de
266
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Klinikum der Friedrich Schiller Universität
Jena
Klinik für Frauenheilkunde und Geburtshilfe
Prof. Dr. med. Ingo Runnebaum, Prof. Dr. med.
Jürgen Weiss, Dr. rer. nat. Ines Hoppe
Bachstraße 18
07743 Jena
T: 03641-933529, F: 03641-933064
[email protected]
www.uni-jena.de/ufk
Praxis für Fertilität – Kinderwunsch- und
Endometriose-Zentrum Berlin
Dr. med. Gülden Halis, Dr. med. David J. Peet,
Dipl.-Biol. Sonja Zeitler
Friedrichstraße 79
10117 Berlin
T: 030-8321190-0, F: 030-8321190-19
[email protected]
www.fertilitaet.de
Zentrum für Reproduktionsmedizin Jena &
Erfurt
PD Dr. med. habil. Heidi Fritzsche,
Dr. med. Andreas Fritzsche
Markt 4
07743 Jena
Juri-Gagarin-Ring 96–98
99084 Erfurt
T: 03641-829610, F: 03641-829681
[email protected]
www.kinderwunschnet.de
www.kinderwunsch-thueringen.de
Wunschkinder Berlin
Dr. Björn Horstkamp, PD Dr. Bernd Krause,
Dr. Petra Rudolph, Dr. Anja BretschneiderSchwarz, Dr. Bettina Pfüller
Uhlandstraße 20–25
10623 Berlin
T: 030-880349056, F: 030-880349050
[email protected]
www.wunschkinder-berlin.de
Kinderwunschzentrum Leipzig-Chemnitz
Dr. med. Fayez Abu Hmeidan, Dr. med. Petra
Jogschies, Dörte Geistert, Laila Shugair
Jakobikirchplatz 4
09111 Chemnitz
T: 0371-5034980, F: 0371-50349881
[email protected]
www.ivf-chemnitz.de
Kinderwunschzentrum Praxisklinik City
Leipzig Standort Chemnitz
Dr. med. Astrid Gabert, Dr. med. Katharina
Bauer, Dr. med. Isabel Schwandt, Jana Sonneck,
Dr. med. Doreen Marx, Dr. rer. nat. Stefanie
Breuer
Flemmingstraße 2a
09116 Chemnitz
T: 0371-433130-0, F: 0371-433130-17
[email protected]
www.ivf-city-leipzig.de
Kinderwunschzentrum am Potsdamer Platz
Dr. med. Hanadi Awwadeh, Dr. med. Anja Mutz
Leipziger Platz 7
10117 Berlin
T: 030-2008950-0, F: 030-2008950-99
[email protected]
www.kinderwunsch-potsdamerplatz.de
MVZ Praxisklinik Sydow am Gendarmenmarkt GmbH
Dr. med. Peter Sydow, Dr. med. Carmen
Sydow, Dr. med. Ulrike Bergmann-Hensel,
Dr. med. Birgit Bestvater, Dr. med. Wibke
Wilkening
Kronenstraße 55–58
10117 Berlin
T: 030-20626720, F: 030-206267218
[email protected]
www.praxisklinik-sydow.de
Kinderwunschzentrum Berlin
Dr. med. Reinhard Hannen, Dr. med. Christian
Friedrich Stoll
Landgrafenstraße 14
10787 Berlin
T: 030-263983-0, F: 030-263983-99
[email protected]
www.kinderwunschzentrum.de
Reproduktionsmedizinisches Zentrum im
Lützow Center GLC
Dr. med. Detlef H. G. Temme
Wichmannstraße 5
10787 Berlin
T: 030-2309980, F: 030-23099830
[email protected]
www.ivf-berlin.de
Kinderwunsch am Wittenbergplatz
Praxis Dr. med. Rolf Metzger
in Praxisgemeinschaft mit Berliner Kinderwunschzentrum
Dr. med. Rolf Metzger, Dr. med. Christiane
Peters, Rainer Mogalle
Tauentzienstraße 6
10789 Berlin
T: 030-21962428, F: 030-23607395
[email protected]
www.berlin-ivf-praxis.de
Kinderwunschzentrum an der Gedächtniskirche
Dr. med. Matthias Bloechle, Dr. med. Silke
Marr
Rankestraße 34
10789 Berlin
T: 030-219092-0, F: 030-219092-99
[email protected]
www.kinderwunsch-berlin.de
D·I·R Annual 2013 – Registry Participants
Kinderwunschzentrum FERA im WenckebachKlinikum
Dr. med. Andreas Jantke, Dr. med. Anna
Stegelmann, Dipl.-Biol. Cornelia Meyer
Wenckebachstraße 23
12099 Berlin
T: 030-760070130, F: 030-760070160
[email protected]
www.kinderwunsch-ivf-berlin.de
Kinderwunschzentrum am Innsbrucker Platz
Berlin
Babette Remberg, Dr. med. Susanne TewordtThyselius, Dr. rer. nat. Thomas Jeziorowski
Hauptstraße 65
12159 Berlin
T: 030-85757930, F: 030-85757935
[email protected]
www.kinderwunschpraxis-berlin.de
Praxis für Kinderwunschtherapie Berlin HelleMitte
Dr. med. Muna Zaghloul-Abu Dakah,
Dr. med. Swetlana Hoffmann
Stendaler Straße 24
12627 Berlin
T: 030-992779-0, F: 030-99277922
[email protected]
www.berliner-kinderwunsch.de
Fertility Center Berlin – Auf dem Gelände der
DRK Kliniken Westend
Prof. Dr. med. Heribert Kentenich, Dr. med.
Gabriele Stief, Dr. med. Andreas TandlerSchneider, Dr. med. Anette Siemann, Dr. med.
Marina Werling, Dr. rer. nat. Ulrike Montag,
Dr. rer. nat. Claus Sibold, Dipl.-Biopharmak.
Jacqueline Ulrich
Spandauer Damm 130
14050 Berlin
T: 030-233208110, F: 030-233208119
[email protected]
www.fertilitycenterberlin.de
Kinderwunschzentrum Potsdam
Dr. med. Kay-Thomas Moeller, Dr. med.
Kathleen Linca, Dr. Manzoor Nowshari
Babelsberger Straße 8
14473 Potsdam
T: 0331-23189292, F: 0331-23189293
[email protected]
www.kinderwunsch-potsdam.de
Praxiszentrum Frauenheilkunde Rostock
PD Dr. med. Heiner Müller, Annette Busecke,
Anja Bossow
Südring 81
18059 Rostock
T: 0381-4401-2030, F: 0381-4401-2031
[email protected]
www.ivf-rostock.de
amedes experts
Facharzt-Zentrum für Kinderwunsch, Pränatale Medizin, Endokrinologie und Osteologie Hamburg
Prof. Dr. med. Michael Ludwig, Prof. Dr. med.
Frank Nawroth, Dr. med. Sabine Neubeck,
PD Dr. med. Barbara Sonntag, Dr. med. Astrid
Dangel, Prof. Dr. med. Klaus Diedrich, Prof.
Dr. med. Christoph Dorn, Dr. med. Cathrin
Grave, Dr. med. Ines Doll, Dr. med. Ute Hugo,
Dr. rer. nat. Beatrice Maxrath
Mönckebergstraße 10
20095 Hamburg
T: 0800-5891688, F: 040-380708310
[email protected]
www.amedes-experts-hamburg.de
MVZ Fertility Center Hamburg GmbH
Prof. Dr. med. Klaus Rudolf, Dr. med. (IL)
Robert Fischer, Dr. med. Kay Christian
Löbbecke, Dr. med. Urte Reinhardt,
Prof. Dr. med. Wolfgang Schulze,
Dr. med. Katja Schwenn
Speersort 4
20095 Hamburg
T: 040-30804400, F: 040-30804952
[email protected]
www.kinderwunsch-hamburg.de
Kinderwunschzentrum Altonaer Straße im
Gynaekologicum Hamburg
Dr. med. Annick Horn, Dr. med. Wolf Michel,
Dr. med. Tim Cordes, Prof. Dr. med. Markus
S. Kupka
Altonaer Straße 59
20357 Hamburg
T: 040-306836-0, F: 040-306836-69
[email protected]
www.ivf-hamburg.de
KinderwunschZentrum Hafencity Hamburg
Dr. med. Ekbert Göhmann, Dr. med. Thomas
Krämer
Überseeallee 1
20457 Hamburg
T: 040-30088-100, F: 040-30088-1010
[email protected]
www.kinderwunsch-hafencity.de
Kinderwunsch Praxisklinik Fleetinsel Hamburg
Tip/Dr. univ. Ist. Semsettin E. Koçak, Dr. med.
Peter List, Cemile Ballnus, Dr. rer. nat. Uwe
Weidner
Admiralitätsstraße 4
20459 Hamburg
T: 040-38605553, F: 040-38605551
[email protected]
www.kinderwunschzentrum-hamburg.de
MVZ Endokrinologikum Hamburg – Zentrum
für Hormon- und Stoffwechselerkrankungen,
Reproduktionsmedizin und Pränatale Medizin
Prof. Dr. med. Christoph Keck, PD Dr. med.
Michael Graf, Dr. med. Tina Osterholz-Zaleski,
Dr. med. Raquel Pozo Ugarte, PD Dr. med.
Sabine Segerer, Dr. med. Nina Wegmann,
Dr. rer. nat. Birthe Nitz, Nicole Becker
Lornsenstraße 4–6
22767 Hamburg
T: 040-30628200, F: 040-30628349
[email protected]
www.endokrinologikum.com
Universitäres Kinderwunschzentrum Lübeck
und Manhagen
Zentrum für Gynäkologische Endokrinologie
und Reproduktionsmedizin am Universitätsklinikum Schleswig-Holstein
Universitäre Kinderwunschzentren GmbH
Prof. Dr. med. Georg Griesinger, M. Sc.,
PD Dr. med. Askan Schultze-Mosgau,
Dr. med. Marion Depenbusch
Ratzeburger Allee 111–125
23562 Lübeck
T: 0451-505-778-10, F: 0451-505-778-299
[email protected]
www.kinderwunsch-luebeck.de
fertilitycenterkiel
Dr. med. Martin Völckers, Dr. med. Nevin Inan
Prüner Gang 15
24103 Kiel
T: 0431-9741333, F: 0431-9741322
[email protected]
www.fertilitycenter.de
Universitäres Kinderwunschzentrum Kiel
PD Dr. med. Sören von Otte, Dr. med. Andreas
Schmutzler, Dr. rer. nat. Heike Eckel
Arnold-Heller-Straße 3, Haus 24
24105 Kiel
T: 0431-5978877, F: 0431-5978878
[email protected]
www.uksh.de/kinderwunsch-kiel
KinderwunschKiel
Dr. med. Kurt Brandenburg, Dr. med. Angela
Carstensen, Dr. med. Kirsten Schem, Dr. sc. agr.
Annette Bonhoff
Im Brauereiviertel 5
24118 Kiel
T: 0431-553433, F: 0431-5192745
[email protected]
www.kinderwunschkiel.de
Team Kinderwunsch Oldenburg
Dr. med. Saif Jibril, Dr. med. Gerhard Pohlig
Leo-Trepp-Straße 5
26121 Oldenburg
T: 0441-2489091, F: 0441-2480611
[email protected]
www.teamkinderwunsch.de
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
267
D·I·R Annual 2013 – Registry Participants
Tagesklinik Oldenburg – Zentrum für Kinderwunschbehandlung
Dr. med. Jörg Hennefründ, Dr. med. Heike
Boppert, Dr. med. Michael Heeder
Achternstraße 21
26122 Oldenburg
T: 0441-922700, F: 0441-9227028
[email protected]
www.tagesklinik-oldenburg.de
Kinderwunschzentrum Ostfriesland
Dr. med. Grita Hasselbach, Dr. rer. nat. Isabell
Motsch
Hafenstraße 6d
26789 Leer (Ostfriesland)
T: 0491-45425-0, F: 0491-45425-10
[email protected]
www.kinderwunschostfriesland.de
Kinderwunsch Bremen
Dr. med. Achim von Stutterheim, Tanja Finger,
Dr. med. Anjarasoa Jung
Emmastraße 220
28213 Bremen
T: 0421-224910, F: 0421-2249122
[email protected]
www.kinderwunschbremen.de
BZF-Bremer Zentrum für Fortpflanzungsmedizin
Dr. med. Olaf Drost, Prof. Dr. med. Ernst
Heinrich Schmidt, Dr. sc. hum. Martin Pinteric
Gröpelinger Heerstraße 406–408
28239 Bremen
T: 0421-6102-1212, F: 0421-6102-1213
[email protected]
www.icsi.de
Team Kinderwunsch Hannover
Dr. med. Nabil Saymé, PD Dr. med. Ulrich A.
Knuth, Dipl.-Biol. T. Krebs
Brühlstraße 19
30169 Hannover
T: 0511-313095, F: 0511-313096
[email protected]
www.team-kinderwunsch-hannover.de
Medizinische Hochschule Hannover
Bereich Gynäkologische Endokrinologie und
Reproduktionsmedizin, OE 6410
Dr. med. Cordula Schippert,
Dr. med. Guillermo-José Garcia-Rocha,
PD Dr. Frauke von Versen-Höynck
Carl-Neuberg-Straße 1
30625 Hannover
T: 0511-532-6099, F: 0511-532-6094
[email protected]
www.mh-hannover.de/11327.html
Kinderwunschzentrum Langenhagen &
Wolfsburg MVZ
Ärztlicher Leiter: Dr. med. Thilo Schill
Ostpassage 9
30853 Langenhagen
Sauerbruchstraße 7
38440 Wolfsburg
T: 0511-972300, F: 0511-9723018
[email protected]
www.kinderwunsch-langenhagen.de
268
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Zentrum für Reproduktionsmedizin und
Humangenetik
Dr. med. Franz-J. Algermissen, Dr. med. Georg
Wilke, Dr. med. Notker Graf, Dr. med. Natascha
Peper
Gartenstraße 18–20
31141 Hildesheim
T: 05121-20679-30, F: 05121-20679-11
[email protected]
www.kinderwunsch-hildesheim.de
Zentrum für Kinderwunschbehandlung und
pränatale Medizin
Dr. med. Dipl.-Biochem. Onno Buurman,
Dr. med. Michael Dumschat, Dr. med. Ralf
Menkhaus
Simeonsplatz 17
32423 Minden
T: 0571-972600, F: 0571-9726099
[email protected],
[email protected]
www.kinderwunsch.net
Praxisklinik Prof. Volz
Prof. Dr. med. Joachim Volz, PD Dr. med.
Stefanie Volz-Köster
Adenauer Platz 7
33602 Bielefeld
T: 0521-9883060, F: 0521-98830622
[email protected]
www.frog.de.com
Bielefeld Fertility-Center – Zentrum für Reproduktionsmedizin und Gynäkologische Endokrinologie
Paul A. Ebert, Dr. med. Karl Völklein, Beata
Szypajlo, Dr. med. Wiebke Rübberdt,
Dr. med. Beate Harms
Werther Straße 266
33619 Bielefeld
T: 0521-101005, F: 0521-101079
[email protected]
www.kinderwunsch-bielefeld.de
MVZ für Reproduktionsmedizin am Klinikum
Kassel
Dr. med. Marc Janos Willi, Dr. med. Oswald
Schmidt, Prof. Dr. (UBsAs) Miguel J.
Hinrichsen
Mönchebergstraße 41–43, Haus F
34125 Kassel
T: 0561-980-2980, F: 0561-9802981
[email protected]
www.kinderwunsch-kassel.de
RepKo – Reproduktionsmedizinisches Kompetenzzentrum am Universitätsklinikum
Gießen & Marburg GmbH
PD Dr. med. Volker Ziller, Prof. Dr. med. Uwe
Wagner
Baldingerstraße
35043 Marburg
T: 06421-58-61330, F: 06421-5867070
Klinikstraße 33
35392 Gießen
T: 0641-98545207, F: 0641-98557099
www.repko-ukgm.de
Kinderwunschzentrum Mittelhessen
Dr. med. Amir Hajimohammad, Berthold Oels
Sportparkstraße 9
35578 Wetzlar
T: 06441-2002020, F: 06441-20020299
[email protected]
www.ivf-mh.de
gyn-medicum
Zentrum für Kinderwunsch
Dr. med. Monica Tobler, Dr. med. Andreas
Schmutzler, Dr. sc. agr. Manuela RopeterScharfenstein
Waldweg 5
37073 Göttingen
T: 0551-41337, F: 0551-41722
www.gyn-medicum.de
Kinderwunschzentrum Göttingen
Dr. med. Rüdiger Moltrecht, Dr. med. Sabine
Hübner, Dr. med. Thomas Welcker, Dr. rer. nat.
Stephanie Mittmann, Dr. med. Peter Schulzeck,
Dr. med. Filiz Sakin-Kaindl
Kasseler Landstraße 25a
37081 Göttingen
T: 0551-99888-0, F: 0551-99888-99
[email protected]
www.kiwu-goettingen.de
Kinderwunschzentrum Magdeburg
Dr. med. Ingrid Nickel, Dr. med. Evelyn
Richter, Dipl. Biol. Katrin Pribbernow
Ulrichplatz 1
39104 Magdeburg
T: 0391-662489-0, F: 0391-662489-29
[email protected]
www.kinderwunschzentrum-magdeburg.de
Otto-von Guericke-Universität Magdeburg
Universitätsklinik für Reproduktionsmedizin
Prof. Dr. med. Prof. h. c. Jürgen Kleinstein,
Carina Strecker, Dr. rer. nat. Katja Seidel
Gerhart-Hauptmann-Straße 35
39108 Magdeburg
T: 0391-6717390, F: 0391-6717389
[email protected]
www.krep.ovgu.de
Kinderwunsch-Kö
Dr. med. Martina Behler, Tanja Emde
Königsallee 63–65
40215 Düsseldorf
T: 0211-3113550, F: 0211-31135522
[email protected]
www.kinderwunsch-koe.de
Interdisziplinäres Kinderwunschzentrum
Düsseldorf MVZ GmbH
Dr. Michael C. W. Scholtes, Ph. D., Dipl. med.
Kersten Marx, Prof. Dr. med. Stefan Kißler,
Dr. med. Petra Hubert, Dr. med. Selma
Yildirim-Assaf, Katja Neldner, Dr. med. Ingrid
Hass-Wenzel, Dr. med. Werner H. Fabry,
Dr. Dipl.-Biol. Ralf Böhm
Völklinger Straße 4
40219 Düsseldorf
T: 0211-90197-0, F: 0211-9019750
[email protected]
www.kids4nrw.de
D·I·R Annual 2013 – Registry Participants
UniKiD – Universitäres interdisziplinäres
Kinderwunschzentrum Düsseldorf
Prof. Dr. med. Jan-Steffen Krüssel, Dr. med.
Nina Bachmann, Dr. med. Daniel Fehr, M.Sc.,
Dr. med. Tanja Freundl-Schütt, PD Dr. med.
Alexandra Hess, Dr. med. Barbara MikatDrozdzynski, Dr. med. Andrea Schanz,
Sonja Schu, Dr. rer. nat. Jens Hirchenhain,
Dr. rer. nat. Dunja M. Baston-Büst
Moorenstraße 5
40225 Düsseldorf
T: 0211-8104060, F: 0211-811-6787
[email protected]
www.unikid.de
novum – Zentrum für Reproduktionsmedizin
Essen – Duisburg
Prof. Dr. med. Thomas Katzorke, Dr. med.
Susanne Wohlers, Najib N. R. Nassar, Dr. med.
Sylvia Bartnitzki, Prof. Dr. med. Peter Bielfeld
Akazienallee 8–12
45127 Essen
T: 0201-29429-0, F: 0201-29429-14
Ärzteforum in der Tonhallenpassage
Friedrich-Wilhelm-Straße 71
47051 Duisburg
T: 0203-713958-0, F: 0203-713958-15
[email protected]
www.ivfzentrum.de
pro-Kindwunsch – Kinderwunschzentrum
Niederrhein
Dr. med. Georg M. Döhmen, Dr. med. Thomas
Schalk, Dr. rer. nat. Ezzaldin Alazzeh
Von-Groote-Straße 175
41066 Mönchengladbach
T: 02161-49686-0, F: 02161-49686-19
Melanchthonstraße 36
47805 Krefeld
T: 02151-150231-0, F: 02151-150231-1
[email protected]
www.pro-kindwunsch.de
REProVita – Kinderwunschzentrum
Recklinghausen
Dr. med. Cordula Pitone
Hertener Straße 29
45657 Recklinghausen
T: 02361-904188-0, F: 02361-904188-41
[email protected]
www.reprovita.de
green-ivf – Grevenbroicher Endokrinologie- &
IVF-Zentrum
Dr. med. Kerstin Friol, PD Dr. med. Christian
Gnoth, Dr. med. Therese Skonieczny
Rheydter Straße 143
41515 Grevenbroich
T: 02181-4915-13, F: 02181-4915-34
[email protected]
www.green-ivf.de
Bergisches Kinderwunschzentrum Remscheid
Dr. med. Johannes Luckhaus, Dr. med. Anke
Beerkotte
Elberfelder Straße 49
42853 Remscheid
T: 02191-79192-0, F: 02191-79192-39
[email protected]
www.kinderwunsch-remscheid.de
Überörtliche Berufsausübungsgemeinschaft
der Kinderwunschzentren Dortmund, Siegen,
Dorsten GbR
Prof. Dr. med. Stefan Dieterle, Dr. med. Andreas
Neuer, Prof. Dr. med. Robert Greb, Dr. med.
Katharina Möller-Morlang, Dr. med. Thomas
von Ostrowski
Olpe 19
44135 Dortmund
T: 0231-557545-0, F: 0231-55754599
Hermelsbacher Weg 41
57072 Siegen
T: 0271-7701810, F: 0271-77018129
Südwall 15
46282 Dorsten
T: 02362-27001, F:02362-27002
[email protected]
www.kinderwunschzentrum.org
Kinderwunschpraxis Gelsenkirchen
Dr. med. Ute Czeromin, Dr. med. Ina WalterGöbel, Dr. med. Kathrin Fißeler
Munscheidstraße 14
45886 Gelsenkirchen
T: 0209-167-1470, F: 0209-167-1471
[email protected]
www.kinderwunsch-gelsenkirchen.de
FCM Fertility Center Münsterland
Dr. med. Ulrich Hilland
Crispinusstraße 12 (am Europaplatz)
46399 Bocholt
T: 02871-23943-43, F: 02871-23943-44
[email protected]
www.fcm-net.de
Kinderwunschpraxis an der Promenade
Mempel & Stratmann
Dr. med. Andrea Mempel, Susanne Stratmann,
Dr. rer. nat. Melanie Rickert-Föhring
Von-Vincke-Straße 14
48143 Münster
T: 0251-414312-0, F: 0251-414312-20
[email protected]
www.kinderwunsch-promenade.de
MVZ Kinderwunsch- und Hormonzentrum
Münster GmbH
Dr. med. Dr. rer. nat. Lutz Belkien, Dr. med.
Caroline Niehoff, Prof. Dr. med. Axel
Kamischke, Dr. med. Juliane Burchard
Hötteweg 5–7
48143 Münster
T: 0251-48267-0, F: 0251-48267-77
[email protected]
www.kinderwunschtherapie.de
UKM Kinderwunschzentrum Universitätsklinikum Münster
PD Dr. med. Andreas Schüring,
Prof. Dr. med. Sabine Kliesch
Albert-Schweitzer-Campus 1, Gebäude D11
48149 Münster
T: 0251-8358280, F: 0251-8348267
[email protected]
www.kinderwunschzentrum.uk-muenster.de
Zentrum für Kinderwunschbehandlung
Osnabrück/Nordhorn
Irene Coordes, Dr. med. Manfred Schneider
Rheiner Landstraße 93–95
49078 Osnabrück
Osnabrücker Straße 1
48529 Nordhorn
T: 0541-404500, F: 0541-4045040
[email protected]
www.kinderwunsch123.de
GMP Frauenheilkunde & Reproduktionsmedizin
Dr. med. Dieter Struller, Dr. med. Christof
Etien
Graf-Salm-Straße 10
50181 Bedburg, Erft
T: 02272-7778, F: 02272-7773
[email protected]
www.kinderwunsch-erft.de
MVZ PAN Institut für Endokrinologie und
Reproduktionsmedizin
Dr. med. Stefan Palm, Dr. med. Irene Pütz,
Dr. med. Mirko Dannhof, PD Dr. med. Dolores
Foth, Dipl. Psych. Anika Nöllgen, Dipl. Psych.
Andrea Gilles, Dr. med. Georg Mansmann,
PD Dr. med. Torsten Schmidt, Prof. Dr. med.
Martina Breidenbach, Dr. med. Sigrid Gerards,
Dr. med. Jürgen Laser, Dr. rer. nat. Bastian
Schäferhoff, Dr. rer. nat. Maike Warnstedt,
Dana Gonzalez M. B.
Zeppelinstraße 1
Neumarkt Galerie
50667 Köln
T: 0221-2776-229, F: 0221-2776-201
[email protected]
www.mvz-pan-institut.de
Klinik und Poliklinik für Frauenheilkunde
und Geburtshilfe der Universität zu Köln
Gynäkologische Endokrinologie und Reproduktionsmedizin
Prof. Dr. med. Peter Mallmann, PD Dr. med.
Gohar Rahimi, Dr. rer. nat. Evgenia Isachenko
Kerpener Straße 34
50931 Köln
T: 0221-478-87550, F: 0221-478-86201
[email protected]
www.frauenklinik.uk-koeln.de/reproduktionsmedizin-kryokonservierung
MVZ Amedes für IVF und Pränatalmedizin
Dr. med. Markus Merzenich
Schönhauser Straße 3
50968 Köln
T: 0221-340307-0, F: 0221-340307-77
[email protected]
www.kinderwunschzentrum-koeln.de
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
269
D·I·R Annual 2013 – Registry Participants
Zentrum für Kinderwunschbehandlung Köln
Eva Schwahn
Schönhauser Straße 3
50968 Köln
T: 0221-3402280, F: 0221-3406017
[email protected]
www.wunschkind-koeln.de
Kinderwunschzentrum Aachen
Dr. med. Klaus Grunwald
Kasernenstraße 25
52064 Aachen
T: 0241-99774141, F: 0241-99774144
[email protected]
www.kinderwunsch-aachen.de
Klinik für Gynäkologische Endokrinologie
und Reproduktionsmedizin
Uniklinik – RWTH Aachen
Prof. Dr. med. Joseph Neulen,
Dr. med. Benjamin Rösing
Pauwelsstraße 30
52074 Aachen
T: 0241-8088971, F: 0241-8082518
[email protected]
www.gyn-endokrinologie.ukaachen.de
Universitätsklinikum Bonn – Gynäkologische
Endokrinologie und Reproduktionsmedizin
Prof. Dr. med. Hans H. van der Ven,
Prof. Dr. med. Katrin van der Ven, Dr. med.
Ulrike Bohlen, Dr. med. Marietta Kühr,
Dipl. hum. biol. Jana Liebenthron
Sigmund-Freud-Straße 25
53127 Bonn
T: 0228-287-19186, F: 0228-28715795
[email protected]
www.kinderwunsch-uni-bonn.de
Praxisklinik für Gynäkologische Endokrinologie und Reproduktionsmedizin
PD Dr. Dr. med. Gernot Paul Prietl, Dr. med.
Monika Prietl, Dr. med. Peter Henschen
Theaterplatz 18
53177 Bonn-Bad Godesberg
T: 0228-3503910, F: 0228-364892
[email protected]
Kinderwunsch Praxisklinik Trier
Dr. med. Mohsen Satari, Prof. Dr. med. Jürgen
P. Hanker
Wissenschaftspark (WIP)
Max-Planck-Straße 15
54296 Trier
T: 0651-97906-0, F: 0651-97906-20
[email protected]
www.kinderwunsch-trier.de
Kinderwunsch Zentrum Mainz
Dr. med. Robert Emig, Dr. med. Christine
Molitor, Prof. Dr. med. Thomas Steck
Fort Malakoff Park
Rheinstraße 4
55116 Mainz
T: 06131-603020, F: 06131-6030210
[email protected]
www.kinderwunschzentrum-mainz.de
270
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Kinderwunschzentrum der Universitätsmedizin Mainz
Prof. Dr. Rudolf Seufert M. Sc., Dr. Ruth
Gomez, Dr. Ch. Haidner
Langenbeckstraße 1
55101 Mainz
T: 06131-173929
[email protected]
www.wunschkind-mainz.de
Kinderwunschzentrum Mittelrhein
Dr. med. Josef Beran, Dr. med. Sebastian
Hagelauer, Dr. med. Birgit Müller, Özgül
Duman, Dr. Valentina Alupei
Marktstraße 83
56564 Neuwied
Viktoriastraße 15
56068 Koblenz
T: 02631-3968-0, F: 02631-3968-29
[email protected]
www.kinderwunsch-mittelrhein.de
repromedicum
Kinderwunschzentrum
Reproduktionsmedizin – Gyn. Endokrinologie
Prof. Dr. med. Dr. med. habil. Ernst
Siebzehnrübl, Dr. med. Anja Weidner
Hanauer Landstraße 328–330
60314 Frankfurt am Main
T: 069-4260770, F: 069-42607710
[email protected]
www.repromedicum.de
Kinderwunschzentrum Frankfurt
Prof. Dr. med. Prof. h. c. Eberhard Merz,
Dr. med. Marie-Theres Swayze, Ines Voß,
Dr. Claas Mehnert
Steinbacher Hohl 2–26, Haus 2
60488 Frankfurt am Main
T: 069-7601-3611, F: 069-76013321
[email protected]
www.kinderwunschzentrumfrankfurt.de
Fertilitätszentrum und Gynäkologische Endokrinologie – Klinik für Frauenheilkunde und
Geburtshilfe
Goethe-Universität
Dr. med. Nicole Sänger, Dr. med. Annette
Bachmann, Dr. Anna Michaelis
Theodor-Stern-Kai 7
60590 Frankfurt am Main
T: 069-6301-5708, F: 069-6301-7120
[email protected]
www.kgu.de/zfg/gyn
Kinderwunsch- und Endometriosezentrum
am Büsing Park
Dr. med. Konstantin Manolopoulos, Dr. med.
Birgit Lühr, Daniela Chemogo, Dr. med. Meral
Gündüz
Herrnstraße 51
63065 Offenbach
T: 069-80907571, F: 069-80907573
[email protected]
www.offenbach-kinderwunsch.de
Kinderwunschzentrum Darmstadt
Dr. med. Aysen Bilgicyildirim, Dr. med.
Matthias Inacker, Prof. Dr. med. Gerhard
Leyendecker
Bratustraße 9
64293 Darmstadt
T: 06151-50098-0, F: 06151-50098500
[email protected]
www.kinderwunschzentrum-da.de
MVZ Kinderwunschzentrum Wiesbaden GmbH
Dr. med. Martin Schorsch, Dr. med. Thomas
Hahn, Dr. med. Geza Adasz, Karin Schilberz,
Dr. med. Michael Amrani
Mainzer Straße 98–102
65189 Wiesbaden
T: 0611-976320, F: 0611-9763210
[email protected]
www.kinderwunschzentrum-wiesbaden.de
Kinderwunsch-Praxis IVF-Saar SaarbrückenKaiserslautern
Dr. med. Lars Happel, Andreas Giebel,
Dr. med. Sascha Tauchert, Dr. med. Anette
Russu, Dr. med. Marika Otte, Dr. rer. medic.
Martin Greuner
Europaallee 15
66113 Saarbrücken
T: 0681-93632-0, F: 0681-93632-10
Maxstraße 13
67659 Kaiserslautern
T: 0631-70431, F: 0631-78568
[email protected]
www.ivf-saar.de
Klinik für Frauenheilkunde, Geburtshilfe
und Reproduktionsmedizin – Universitätskliniken des Saarlandes
Prof. Dr. med. E.-F. Solomayer, Dr. med. Peter
Rosenbaum, Prof. Dr. Dr. M. E. Hammadeh,
Dr. med. Kathrin Abel, Dr. med. Daniel
Benndorf, Dr. med. Peter Jankowski,
Dr. med. Simona Moga
Kirrbergstraße 1
66421 Homburg
T: 06841-1628213, F: 06841-1628061
[email protected]
www.uniklinikum-saarland.de/einrichtungen/
kliniken_institute/frauenklinik/
Kinderwunschzentrum Ludwigshafen
Dr. med. Tobias Schmidt, Dr. med. Elena
Hartschuh, Dr. med. Claudia Schmidt,
Dr. rer. nat. Nicole Hirschmann
Ludwigstraße 54b
67059 Ludwigshafen
T: 0621-59298688, F: 0621-59298690
[email protected]
www.kinderwunschzentrum-ludwigshafen.de
Kinderwunschzentrum der Universitätsmedizin Mannheim
Prof. Dr. med. Marc Sütterlin, Dr. med. Regine
Schaffelder, Dr. med. Julia Rehnitz, Dr. med.
Jade Mayer, Dr. sc. hum. Monika Gentili
Theodor-Kutzer-Ufer 1–3
68167 Mannheim
T: 0621-383-3638, F: 0621-383-3814
[email protected]
www.umm.de/64.0.html
D·I·R Annual 2013 – Registry Participants
Viernheimer Institut für Fertilität
PD Dr. med. S. Volz-Köster, Dr. med. C. Nell
Walter-Gropius-Allee 2
68519 Viernheim
T: 06204-918290, F: 06204-9182910
[email protected]
www.vif-kinderwunsch.de
Kinderwunschzentrum Heidelberg
Dr. med. Waltraud Parta-Kehry, Dr. sc. hum.
Suat Parta, Friederike Tesarz, Dr. med. Daniela
Seehaus, Dr. med. Christina Thöne
Römerstraße 3
69115 Heidelberg
T: 06221-89300-0, F: 06221-89300-20
[email protected]
www.kwz-hd.de
Abt. für Gynäkologische Endokrinologie und
Fertilitätsstörungen – Universitätsklinikum
Heidelberg
Prof. Dr. med. Thomas Strowitzki, Prof. Dr.
Bettina Toth, PD Dr. med. Ariane Germeyer,
Dr. med. Sabine Rösner, Dr. med. Julia Rehnitz,
Dr. med. Verena Holschbach, Dr. rer. nat. Inge
Eberhardt, Dr. rer. nat. Jens Dietrich
Im Neuenheimer Feld 440
69120 Heidelberg
T: 06221-567910, F: 06221-564099
[email protected]
www.klinikum.uni-heidelberg.de/Kinderwunschambulanz.583.0.html
Kinderwunsch-Zentrum Stuttgart
Prof. Dr. med. Dieter H. A. Maas, Dr. med.
Friedrich Gagsteiger, Dr. med. Klaus Bühler,
Dr. med. Nina Kircher, Dr. med. Lisa Beiglböck,
Dr. med. Gerhild Weiß
Friedrichstraße 45
70174 Stuttgart
T: 0711-997806-0, F: 0711-997806-10
[email protected]
www.kidz-stuttgart.de
Kinderwunsch-Zentrum-Stuttgart, Praxis Villa
Haag
Dr. med. Dieter B. Mayer-Eichberger
Herdweg 69
70174 Stuttgart
T: 0711-221084, F: 0711-221085
[email protected]
www.kinderwunschpraxis.de
Kinderwunschzentrum Ludwigsburg
Dr. med. Andreas Ott, Dr. med. Annette
Schmid, Dr. med. Katja Becker
Pflugfelder Straße 22
71636 Ludwigsburg
T: 07141-688760, F: 07141-688769
[email protected]
www.kinderwunschzentrum-ludwigsburg.com
KinderwunschPraxis Dres. Göhring
Dr. med. Ulrich Göhring, Dr. med. Inés Göhring
Hagellocher Weg 63
72070 Tübingen
T: 07071-94663-0, F: 07071-94663-99
[email protected]
www.kinderwunschpraxis.com
IVF-Zentrum der Universitäts-Frauenklinik
Tübingen
Dr. med. Melanie Henes
Calwerstraße 7
72076 Tübingen
T: 07071-2983117, F: 07071-292250
[email protected]
www.uni-frauenklinik-tuebingen.de
Kinderwunschzentrum Aalen
Dr. med. Rainer Rau, Dr. med. Birgit Schröppel,
Dr. rer. nat. Roland Eid
Weidenfelder Straße 1
73430 Aalen
T: 07361-62021, F: 07361-62026
[email protected]
www.kinderwunsch-aalen.de
IVF-Zentrum Esslingen
Praxis Dr. J. E. Costea
Dr. med. Johann Emil Costea, Dipl.-Ing.
Luminitza Costea, Dr. rer. nat. Michael Troge
Martinstraße 15
73728 Esslingen
T: 0711-31059160, F: 0711-31059161
[email protected]
www.ivf-praxis.com
Centrum für Kinderwunsch Pforzheim
Verena Peuten
Zerrenner Straße 22–24
75172 Pforzheim
T: 07231-2808280, F: 07231-28082888
[email protected]
www.kinderwunsch-pforzheim.de
Kinderwunschzentrum Karlsruhe
Arbeitsgemeinschaft für Fortpflanzungsmedizin
Hans-Jürgen Gräber, Dr. med. Daniela Plathow,
Dr. Frank Tetens, Laborärzte Dr. Ehrfeld &
Kollegen, Humangenetik Dr. Schlüter
Waldstraße 2
76133 Karlsruhe
T: 0721- 8246700, F: 0721-82467090
[email protected]
www.ivf-programm.de
Klinikum Mittelbaden
Zentrum für Minimal Invasive Gynäkologie,
Endometriose und Reproduktionsmedizin
Prof. Dr. med. Wolfgang Küpker
Engelstraße 39
76437 Rastatt
T: 07222-389-5400, F: 07222-389-65400
[email protected]
www.kinderwunschzentrum-mittelbaden.de
Kinderwunsch Bodensee
Dr. med. Andreas Heine, Dr. med. Katja
Drescher, Dr. Angela Panhans
Maggistraße 5
78224 Singen
T: 07731-912999-0, F: 07731-912999-99
[email protected]
www.endlichnachwuchs.de
Centrum für gynäkologische Endokrinologie
und Reproduktionsmedizin Freiburg (CERF)
Dr. med. Rudolf Weitzell, Dr. med. Maria
Thiemann, PD Dr. med. Birgit Wetzka,
Prof. Dr. med. Franz Geisthövel,
Dr. med. Veronika Wolk
Bismarckallee 7f
79098 Freiburg
T: 0761-20743-0, F: 0761-32111
[email protected]
www.kinderwunsch-hormone.de
Universitätsklinikum Freiburg
Klinik für Frauenheilkunde – Abteilung für
Endokrinologie und Reproduktionsmedizin
Dr. med. R. Schwab, Dr. rer. nat. B. Acar-Perk
Hugstetter Straße 55
79106 Freiburg
T: 0761-270-31500, F: 0761-270-29120
[email protected]
www.uniklinik-freiburg.de/frauenheilkunde/
endokrinologie-und-reproduktionsmedizin.
html
Reproduktionsmedizin München
Medizinisches Versorgungszentrum
Partnerschaftsgesellschaft
Dr. med. Walter Bollmann, Dr. med. Thomas
Brückner, Dr. med. Ulrich Noss, Dr. med.
Daniel Noss, PD Dr. med. Robert Ochsenkühn,
Dr. med. Barbara Wiedemann
Ärzte für Laboratoriumsmedizin Dr. med.
Gerhard Noss, Risto Gjavotchanoff
Tal 11
80331 München
T: 089-242295-0, F: 089-242295-60
[email protected]
www.ivf-bbn.de
kïz) kinderwunsch im zentrum
Praxis für gynäkologische Endokrinologie und
Reproduktionsmedizin
PD Dr. med. Roxana Popovici, Dr. med. Anja
Kuhlmann
Bayerstraße 3
80335 München
T: 089-4522178-0, F: 089-4522178-45
[email protected]
www.kiiz.de
Zentrum für Gynäkologische Endokrinologie
und Reproduktionsmedizin
Klinikum der LMU München-Innenstadt
Prof. Dr. med. Christian J. Thaler, Dr. med. Nina
Rogenhofer, Dr. Panos Papadopoulos Ph. D.,
Prof. Dr. med. Klaus Friese
Maistraße 11
80337 München
T: 089-4400-54214, F: 089-4400-54918
www.kinderwunsch-uni-muenchen.de
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
271
D·I·R Annual 2013 – Registry Participants
Kinderwunsch Zentrum an der Oper
Dr. med. Helmut Lacher, Dr. med. Jörg Puchta,
PD Dr. med. Hans-Ulrich Pauer, Dr. med. Silke
Michna
Maximilianstraße 2a
80539 München
T: 089-547041-0, F: 089-547041-34
[email protected]
www.hormonzentrum.de
Kinderwunsch Centrum München (MVZ)
Dr. med. Klaus Fiedler, Dr. med. Gottfried
Krüsmann, Prof. Dr. Dr. med. habil. Wolfgang
Würfel, Dr. med. Irene von Hertwig, Dr. med.
Jan Krüsmann, Ina Laubert, Osama Meri,
Dr. med. Claudia Santjohanser, Sabine Völker
Lortzingstraße 26
81241 München
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[email protected]
www.ivf-muenchen.de
Hormon- und Kinderwunschzentrum
Klinikum der LMU München-Grosshadern
Prof. Dr. med. Christian J. Thaler, Prof. Dr. med.
Klaus Friese, Dr. rer. nat. Viktoria von
Schönfeldt
Marchioninistraße 15
81377 München
T: 089-4400-76825, F: 089-4400-73844
www.kinderwunsch-uni-muenchen.de
GMP Frauenärzte Prof. Berg, Dr. Lesoine
Reproduktionsmedizin in Bogenhausen
Prof. Dr. med. Dieter Berg, Dr. med. Bernd
Lesoine
Prinzregentenstraße 69
81675 München
T: 089-414240-0, F: 089-414240-11
[email protected]
www.ivf-muenchen.com
Kinderwunsch Centrum Chiemsee
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Stachl
Hochriesstraße 21
83209 Prien am Chiemsee
T: 08051-5050, F: 08051-63499
[email protected]
www.kinderwunsch-chiemsee.de
IVF-Zentrum Augsburg
GMP Dres. Hiller, Bauer, Kraus, SteinfeldBirg
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Thomas Bauer, Dr. med. Harald Kraus,
Dr. med. Dieter Steinfeld-Birg
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KinderWunschKempten (KWK)
Zentrum für Reproduktionsmedizin am
Klinikum Kempten
Prof. Dr. med. Ricardo Felberbaum, Dr. med.
Anke Brössner, Dr. med. Elisabeth Büchele,
Dipl. Biol. Mohammad Kousehlar
Robert-Weixler-Straße 50
87439 Kempten
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[email protected]
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Strehler, Prof. Dr. med. Wolfgang Hütter
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89073 Ulm
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[email protected]
www.kinderwunsch-ulm.de
Kinderwunschzentrum Erlangen
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Haas
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91052 Erlangen
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[email protected]
www.kinderwunschzentrum-erlangen.de
Universitäts-Fortpflanzungszentrum Franken
(UFF)
Prof. Dr. Matthias W. Beckmann, PD Dr.
Susanne Cupisti, Prof. Dr. Ralf Dittrich,
PD Dr. Stefan P. Renner, MBA
Universitätsstraße 21–23
91054 Erlangen
T: 09131-85-33553, F: 09131-85-33456
[email protected]
www.reproduktionsmedizin.uk-erlangen.de
Universitätsfrauenklinik und Poliklinik Ulm
Zentrum für Reproduktionsmedizin und
Gynäkologische Endokrinologie
PD Dr. med. Katharina Hancke
Prittwitzstraße 43
89075 Ulm
T: 0731-50058663, F: 0731-50058664
[email protected]
www.uni-ulm.de/ivf
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Am Klinikum St. Marien Amberg
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[email protected]
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Dr. med. Nilofar Huzurudin, Dr. med. Verena
Domschat, Julia Koglin
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89077 Ulm
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[email protected]
www.kwz-ulm.de
KITZ Regensburg – KinderwunschTherapie
im Zentrum
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Gaßner
Hemauerstraße 1
93047 Regensburg
T: 0941-992577-0, F: 0941-992577-23
[email protected]
www.kitz-regensburg.de
Kinderwunsch und Frauen-Hormon Centrum
Nürnberg
Dr. med. Joachim Neuwinger, Dr. med.
Barbara Munzer-Neuwinger, Prof. Dr. med.
Peter Licht
Agnesgasse 2–4
90403 Nürnberg
T: 0911-2355500, F: 0911-2355516
[email protected]
www.kinderwunschzentrum-nuernberg.de
Kinderwunschzentrum profertilita
Prof. Dr. med. Monika Bals-Pratsch, M. Sc.,
Dr. med. Angelika Eder, M. Sc.
Hildegard-von-Bingen-Straße 1
93047 Regensburg
T: 0941-89849944, F: 0941-89849945
[email protected]
www.profertilita.de
GMP Dres. Hamori, Behrens, Hammel
Dr. med. Miklos Hamori, Dr. med. Rolf
Behrens, Dr. med. Andreas Hammel
Nürnberger Straße 35
91052 Erlangen
T: 09131-89520, F: 09131-205410
[email protected]
www.ivf-erlangen.de
Kinderwunschzentrum Niederbayern
Dr. med. Hans-Joachim Kroiss, Dr. med.
Samuel Dadze, Dr. IM Tem. Elfriede
Bernhardt
Stadtfeldstraße 50
94469 Deggendorf
T: 0991-29799332, F: 0991-29799331
[email protected], [email protected]
www.kinderwunsch-niederbayern.de
D·I·R Annual 2013 – Registry Participants / Sponsors
Klinik am Hofgarten – Kinderwunsch-Zentrum
Bayreuth
Dr. med. Dr. phil. Stefan Todorow,
Dr. med. Erika Schwarz
Richard-Wagner-Straße 34–36
95444 Bayreuth
T: 0921-7454440, F: 0921-74544410
[email protected]
www.ivf-bayreuth.de
Zentrum für Reproduktionsmedizin, Medizinische Genetik und Pränataldiagnostik
Dr. med. Reinhard Mai, Dr. med. Wolfgang
Schmitt, Dr. med. Lore Mulfinger
Juliuspromenade 7
97070 Würzburg
T: 0931-321230, F: 0931-3212377
[email protected]
www.drs-mai-schmitt-mulfinger.de
Universitätsklinikum Würzburg
Frauenklinik und Hebammenschule
Zentrum für gynäkologische Endokrinologie
und Reproduktionsmedizin
Prof. Dr. med. Ursula Zollner, Dr. med.
Michael Schwab, Dr. rer. nat. Claudia Staib
Josef-Schneider-Straße 4
97080 Würzburg
T: 0931-201-25619, F: 0931-201-25406
[email protected]
www.frauenklinik.uni-wuerzburg.de
Sponsors
Without generous support, publishing this Annual would not have been possible.
Our gratitude goes to:
FERRING Arzneimittel GmbH, Kiel
www.ferring.de
4,500 EUR
Merck Serono GmbH, Darmstadt
www.merckserono.de
4,500 EUR
MSD Sharp & Dohme GmbH, Haar bei München
www.msd.de
4,500 EUR
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
273
Options for Fertility Preservation in Cancer Patients
R. Dittrich, L. Lotz, J. Hackl, S. Nichols-Burns, T. Hildebrandt, H. Schneider, I. Hoffmann, M. W. Beckmann
Little attention was given to fertility loss as a potential consequence of radio-/chemotherapy in the past. In recent years, interest in fertility preserving measures for cytotoxic therapy has risen sharply and includes the establishment of the network FertiPROTEKT. Cryoconservation of sperm is an established method of fertility preservation for males. Options for females include transposition of the gonads prior to radiotherapy, protection of the gonads using gonadotropin-releasing hormone (GnRH) analogues, and cryoconservation of embryos, oocytes, and ovarian tissue. Although most of the aforementioned methods
are currently regarded as experimental, they make it possible for affected women to have children after recovering from disease. Fertility-preserving procedures should therefore be offered to all patients facing fertility loss before cytotoxic treatment is administered. Rapid and simultaneous collaboration with a
specialized fertility center and provision of correct and detailed information for the patient are of extreme importance. This article discusses the importance
of fertility-preserving methods for the specialty of gynecology and outlines the currently available techniques. J Reproduktionsmed Endokrinol 2014; 11
(5–6): 274–9.
Key words: fertility preservation, family planning, cancer, ovary
 Introduction
Increasing survival rates for cancer patients and an increasing awareness of the
quality of life after chemo-/radiotherapy
have focused attention on the preservation of fertility after cancer treatment.
Due to great progress in reproductive
medicine, measures that make it possible
for affected women to have children after
recovering from the disease can now be
offered.
The effects of malignant disease on gonadal function are caused in most cases
indirectly by the influence of cytotoxic
therapy. Chemotherapy and/or radiotherapy very often lead to partial or complete
impairment of the ovaries and spermatozoa, severely reducing or eliminating
fertility. The gonadotoxic effects are
strongly dependent on the patient’s age
(older age correlating to higher risk), the
type, dose and duration of chemotherapy
and radiation therapy (Table 1, 2).
The aim of the present article is to provide basic information on fertility-preserving measures and to enhance awareness among medical staff treating affected patients that such measures are available. Our main focus is on fertility preservation for women, but options for men
are also mentioned.
 Options for Fertility Preservation in Women
In general, diseases that require treatment that is gonadotoxic represent an in-
Table 1. Infertility after Treatment with Different Cytotoxic Drugs
Toxic effect on spermatozoa
Initiation of ovarian dysfunction
High risk
– Chlorambucil
– Cyclophosphamid
– Nitrosoharnstoff
– Busulfan
– Fludarabin
– Procarbazin
– CCNU
– Chlorambucil
– Cyclophosphamid
– Busulfan
– CCNU
– Mitomycin C
Moderate risk
– Doxorubicin
– Vinblastin
– Cytarabin
– Cisplatin
– Topoisomerase-I-Hemmstoffe
– Doxorubicin
– Vinblastin
– Cisplatin
– Topoisomerase-I-Hemmstoffe
Low risk
– Methotrexat
– 5–Fluorouracil
– 6–Mercaptopurin
– Vincristin
– Methotrexat
– 5–Fluorouracil
– 6–Mercaptopurin
– Vincristin
Unknown risk
– Bleomycin
– Etoposid
– Gemcitabin
– Taxane
– Oxaliplatin
– Irinotecan
– Antibody
– Small molecules
– Etoposid
– Nitrosoharnstoffe
– Gemcitabin
– Taxane
– Oxaliplatin
– Irinotecan
– Antibody
– Small molecules
Table 2. Radiotoxicity and Ovarian Insufficiency. Adapted from [Demewood MD
1986]
Risk of Sterility
Ovarian radiation dosage (Gy) (Patient age in years [y])
No effect
Some risk
60%
70%
100%
100%
0.6
1.5
2.5–5 (15–40y)
5–8 (15–40y)
> 8 (15–40y)
2.5–5 (> 40y)
Received: June 20, 2014; accepted after revision: September 1, 2014.
From the Department of Gynecology, Erlangen University Hospital, University of Erlangen-Nuremberg
Correspondence: Prof. Dr. rer. nat. Ralf Dittrich, Department of Gynecology, Erlangen University Hospital, D-91054 Erlangen, Universitätsstraße 21–23;
e-mail: [email protected]
274
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Options for Fertility Preservation in Cancer Patients
dication for measures to protect the ovary. Fertility-preserving measures have to
be customized to match the patient’s individual clinical situation. Aspects to be
taken into account include the time available before the start of oncological therapy, patient’s age, relationship status, potential ovarian involvement in the cancer,
and gonadotoxic measures that are to be
used (Fig. 1). If possible, it should be ensured that operations are carried out as
fertility-conserving surgeries. In terms of
radiotherapy, attention must be paid to
sufficient gonad protection by the choice
of treatment fields and lead aprons.
Transposition of the Ovaries
(Ovariopexy)
In patients with Hodgkin or non-Hodgkin lymphomas, cervical carcinoma,
colorectal carcinoma, or other solid malignancies which require radiotherapy to
the pelvis, the ovaries can be surgically
repositioned away from the radiotherapy
field before starting treatment. The ovaries are laparoscopically mobilized after
transection of the ovarian ligaments or
by opening the retroperitoneum via bilateral division of the peritoneum along the
infundibulo-pelvic ligament, so that a
transection of the fallopian tube is not
necessary in most cases. Subsequently,
the mobilized ovary is fixed cranio-laterally to the peritoneum of each paracolic
gutter. Ovaries can be marked with radiopaque metal clips, so their location can
be checked during treatment. The proportion of patients < 40 years of age who
recover regular ovulatory cycles after
radiotherapy with this technique is up to
85% [2]. The success rate with this method
depends on applied radiation dosage and
scattered radiation. Rare complications
include pain during ovulation, cyst formation, thrombosis, and ischemia [3].
GnRH Analogues
Gonadotropin-releasing hormone (GnRH)
agonists may be utilized to inhibit the release of follicle-stimulating hormone in
postpubertal women, inducing transient
hypogonadotropic hypogonadism and
placing the ovaries in a “resting” state.
Hereby, it is anticipated that follicles can
be protected and fertility be preserved.
The latest meta-analysis including only
randomized controlled studies (n = 6) reported a reduced rate of premature ovarian failure with GnRH agonist administration, with an odds ratio of 3.5 [4]. Preliminary results of the most recent study
Figure 1. Planned Approach at German University Reproductive Centers. Mod. from [1]. * CHT = Chemotherapy treatment
of LHRH analog during chemotherapy
to reduce ovarian failure in early stage,
hormone receptor-negative breast cancer
(Prevention of Early Menopause Study[POEMS-] SWOG S0230) show a reduced rate of premature ovarian failure
by using LHRH analogue (OR = 0.3;
95%-CI: 0.10–0.87; p = 0.3 [unadjusted
analyses]) [5]. On the other hand, other
studies on administration of GnRH agonists in adjuvant chemotherapy for breast
cancer and lymphoma did not demonstrate a significant benefit [6, 7]. When
used, GnRH analogues should be administered at least 1 week before starting
chemotherapy due to the initial increase
in the release of gonadotropins (known
as the “flare-up” effect), and administration should continue for at least 1–2
weeks after the last chemotherapy cycle.
If the time window before the start of
chemotherapy is less than a week, it is
possible to combine GnRH agonists with
GnRH antagonists in order to reduce
flare-up [8]. Side effects of GnRH analogues can include menopausal symptoms (although this is also possible with
chemotherapy alone) and a reduction in
bone mass if the drug exposure is longer
than 6 months. It should also be noted
that possible negative effects of GnRH
analogues on the prognosis for patients
with estrogen receptor-positive diseases
(e.g., breast carcinoma) have not yet
been clarified. This method is currently
regarded as safe, noninvasive, and easy
to administer [9] and may be considered
on an individual basis in combination
with other fertility-protecting measures
if possible. Statements regarding the
chance of pregnancy cannot be made at
the present time and must be discussed in
detail during the information talk with
the patient. Further randomized prospective studies are lacking.
Cryopreservation of Unfertilized
and Fertilized Oocytes
Prophylactic cryopreservation of unfertilized and fertilized oocytes is a wellestablished assisted reproductive technique (ART) and is especially applicable
in the frame of fertility preservation prior
to gonadotoxic therapy. Ovarian stimulation to harvest oocytes can be carried out
with most postmenarchal women aged
 40 years. With the development of new
protocols, stimulation can begin at any
point during the menstrual cycle of the
patient, so that the working time frame
requires only 2 weeks prior to start of
cytotoxic therapy. Use of GnRH-antagonists and ovulation induction with a
GnRH-agonist prevents ovarian hyperstimulation syndrome, which would require postponement of chemotherapy.
Cytotoxic therapy can begin 1–2 days
after follicle puncture [10].
Freezing pronuclear stage zygotes using
traditional slow cryopreservation has
been well established, especially in
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
275
Options for Fertility Preservation in Cancer Patients
countries like Germany where planned
cryopreservation of human embryos by
nuclear fusion is prohibited by law. Survival rates after conventional slow freezing of zygotes are between 70 and 80%.
Clinical pregnancy rates amount to 18%
with an implantation rate of 10% per
transferred embryo [11, 12]. Survival
rate for vitrified zygotes is > 90% with a
cleavage rate of 80% on day 2 and blastocyst formation rate on day 5 > 30%
[13]. Al Hasani et al have published clinical pregnancy and implantation rates of
30% and 17% [11].
Another ART is the cryopreservation of
unfertilized oocytes. Despite publication
of the first birth after cryopreservation of
unfertilised oocytes with a slow freezing
protocol in humans 1986 [14], this technique was considered controversial due
to the low survival rates of the cells.
Based on improved survival rates due to
slight modifications of slow freezing and
vitrification protocols, the cryopreservation of unfertilized oocytes now represents an effective ART. Pregnancy rates
can be achieved comparable to those resulting from IVF treatment using fresh
eggs [15]. In a randomized controlled trial, pregnancy rate was compared with
surplus slow freeze and vitrified oocytes.
Results demonstrated that vitrification
leads to a better survival of oocytes (81%
vs. 67%; p < 0.001), higher rate of fertilization (77% vs 67%; p = 0.03), and
higher pregnancy rate per thawed oocytes compared to slow freeze oocytes
(5.2% vs 1.7%; p = 0.03) [16]. However,
other clinics report equivalent success
of the two freezing methods in observational studies [17], and it is likely that
clinic-specific success rates vary with
different cryopreservation protocols. Today, over 1000 children worldwide have
been born through cryopreservation of
unfertilized oocytes. Based on available
data, no increased risk of congenital
anomalies has been observed [18]. The
malformation rate of children born by
cryopreserved oocytes does not differ
from those after spontaneous concep-
tion. Due to these advances, the American Society for Reproductive Medicine
no longer considers cryopreservation of
unfertilised oocytes experimental, but an
established method for retaining fertility
[19].
Risks associated with ovarian stimulation are low. In the complication register
of the FertiPROTEKT network no shift
of chemotherapy due to complication
was required in 205 stimulations. In patients with hormone-dependent tumors,
such as hormone receptor-positive breast
cancer or hormone-dependent genital tumors, ovarian stimulation should be critically discussed because of increased
estradiol levels. In consultation with the
oncologist, gonadotropins, antiestrogens
(e.g., tamoxifen) or aromatase inhibitors
(e.g., letrozole) could be administered
during ovarian stimulation to reduce the
unwanted rise of estradiol and to carry
out an antiestrogenic effect on the tumor
cells with a reduced risk of cancer progression [10].
One point against cryopreservation of
zygotes or unfertilized oocytes as an option for fertility preservation in cancer
patients is the need of hormonal stimulation to achieve more than 1 oocyte.
Stimulation is accompanied with a delay
of the chemotherapy because normally
the start of the stimulation procedure,
which already needs at least 10 days, is
at the beginning of the follicular phase.
When the patient is in the luteal phase, it
is necessary to wait until bleeding occurs. An alternative is already to initiate
the ovarian stimulation in the luteal
phase together with the administration of
Gonadotropin-Releasing Hormone antagonist (GnRH-antagonist), which is
administered to induce immediate luteolysis. The success of this application was
already shown by von Wolff et al in 2009
[20] and recently at the Meeting of the
European Society of Human Reproduction and Embryology in 2014, where the
results of 674 cases of luteal phase stimulation were presented [21].
In-vitro maturation
In-vitro maturation (IVM) involves obtaining immature oocytes, maturing
them, and then fertilizing them. Immature oocytes from small antral follicles
are obtained by transvaginal aspiration
after short stimulation with follicle-stimulating hormone (FSH) and/or human
chorionic gonadotropin (HCG), if necessary. Harvested oocytes are matured invitro into fertilizable metaphase II oocytes and can then be cryopreserved. It is
unnecessary to expose patients to highdose gonadotropin therapy with this
method, and the time required before follicular puncture is shorter than with conventional stimulation, making it easier to
avoid a delay in the start of chemotherapy. Immature oocytes can also be obtained during processing of biopsied
ovarian tissue. IVM of oocytes during
cryopreservation of ovarian tissue offers
an additional option of fertility preservation without additional risk and expense
for the patient [22]. However, with the
exception of results from a few research
groups, data on pregnancy rates with this
procedure are still very limited and the
reported rates are lower than those with
conventional in-vitro fertilization (IVF)
[23, 24].
Cryopreservation of Ovarian
Tissue
Cryopreservation of ovarian tissue has
been investigated as a method of fertility
preservation for more than a decade and
has recently achieved considerable success. Over 25 live births have been reported following transplantation of cryopreserved ovarian tissue ([25] and personal communication). Technically, ovarian extraction is a simple procedure.
Ovarian tissue can be obtained using
minimally invasive techniques during
laparoscopy, with unilateral ovariectomy
or partial ovariectomy. Cryopreservation
of ovarian tissue can be carried out independent of menstrual phase and, therefore, does not lead to any delay in oncological therapy (Table 3). In centers that
offer cryopreservation of ovarian tissue,
Table 3. Comparison of the Fertility Preservation Options in Women
Cryopreservation of ovarian tissue
Cryopreservation of unfertilized oocytes
Cryopreservation of fertilized oocytes
276
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Characteristics
Time required
Pregnancy rate
Laparoscopy, retransplantation
Stimulation
Partner, stimulation
Immediately
10–14 d
10–14 d
Over 25 live births worldwide
20–30%
20–35%
Options for Fertility Preservation in Cancer Patients
Table 4. Comparison of the Fertility Preservation Options in Women
Advantages
Disadvantages
– Risk that tumor cells may be reimplanted
– Limited experience
Cryopreservation of
unfertilized oocytes
– No treatment delay
– Only way to preserve fertility in prepubertal girls
– Treatment of women without a partner
– No unwanted estrogen peak
– Can be used in chemo- and radiotherapy
– Restoration of fertility and endocrine function
– Can be used in chemo- and radiotherapy
– Treatment of women without a partner
Cryopreservation of
fertilized oocytes
– Established method with high pregnancy rate
– Can be used in chemo- and radiotherapy
Cryopreservation
of ovarian tissue
the procedure can be performed 1 day after the patient’s first visit. After the tissue
has been removed, it can be processed
immediately or transferred in specific
transportation containers to a center that
is specialized in the cryopreservation of
ovarian tissue with an associated cryobank.
A transport duration of 4–5 hours before
cryopreservation is possible without any
problems [26]. In addition, the viability
of the tissue appears also to be preserved
for longer periods of time (overnight
transport), as the first live birth in Germany after re-transplantation of cryopreserved ovarian tissue has demonstrated
[27].
In general, cryopreservation of ovarian
tissue involves similar cryogenic processes as those utilized for cryopreservation
of oocytes or embryos. “Slow freezing”
is currently recommended for freezing
ovarian tissue due to current higher efficiency with this method. In all previously
published births following retransplantation of cryopreserved ovarian tissue, the
tissue underwent slow freezing [22]. Of
note, however, experimental tests demonstrate increasingly better results for vitrification [28].The main purpose of cryopreservation of ovarian tissue is to preserve viable ovarian tissue for potential
reimplantation if ovarian function fails
following cancer treatment. Ovarian tissue is usually reimplanted at the natural
site (orthotopically), in a peritoneal pocket, or in the residual ovarian bed, in order
to allow spontaneous conception. The
first reimplantation of ovarian tissue in
Germany was performed in 2007 at the
Department of Gynecology at Erlangen
University Hospital [29]. Resumption of
hormonal function in reimplanted tissue
has now been documented on many occasions, and there have been over 25 recently reported births following orthotopic
reimplantation of cryoconserved ovarian
tissue. The first birth after reimplantation
of cryoconserved ovarian tissue in Germany occurred on October 10, 2011 [30].
The first international surveys of birth
rate per ovarian tissue transplantation report a success rate of approximately 15%,
which is likely to increase in the future.
The possibility that tumor cells may be
concurrently reimplanted is a problem
that must be discussed with the patient.
To date, there have been no cases in
which this has been confirmed, although
considerable caution is advised regarding cryopreserved tissue from patients
with leukemia, borderline ovarian tumor,
or with a high risk of ovarian metastases
(e.g., in adenocarcinoma of the cervix or
stage III–IV breast cancer) [31, 32]. An
option for these patients could be the
maturation of follicles in vitro without
transplantation. The ability of primordial
follicles of ovarian tissue to fully mature
in vitro and produce fertilizable, viable
ova has only been demonstrated in a few
animal model reports. Total in-vitro
maturation of human oocytes from cryopreserved ovarian tissue is not yet possible [33]. However, it is quite conceivable
that in the next few years this technique
will be successful in humans [34].
Another option is ovarian tissue xenotransplantation. Ovarian tissue is transplanted into a surrogate host, such as immunodeficient mice (e.g., SCID mice),
which do not have rejection reactions
against foreign tissue. Follicles that mature can be punctured to obtain oocytes.
This method has been used experimentally to test the vitality of frozen ovarian
– Treatment delay
– Not for prepubertal girls
– Unwanted estrogen peak
– Partner
– Treatment delay
– Not for prepubertal girls
– Unwanted estrogen peak
tissue and to assess any malignant contamination [32] (Table 4).
Combination of Different Techniques
To increase the effectiveness of individual measures, a combination of the described fertility preservation strategies
could be considered. For example, when
2 weeks are left before starting chemotherapy, ovarian stimulation could be
performed and on the day of oocyte retrieval, ovarian tissue could also be harvested for cryopreservation at the same
time [35]. Removing ovarian tissue first
and starting ovarian stimulation approximately 1–2 days later is an alternative
approach. The partial removal of ovarian
tissue does not substantially affect the
average number or quality of oocytes retrieved after ovarian stimulation [36].
Moreover, GnRH analogues could also
be administered simultaneously with the
induction of ovulation in these patients,
thereby protecting remaining follicles.
 Options for Fertility Preservation in Men
In men, cryopreservation of ejaculate or
testicular tissue are established means of
creating a fertility reserve. A therapeutically effective method that protects testicular function from gonadotoxic effects
of chemotherapy or radiotherapy has to
be developed [37]. Hormonal suppression of spermatogenesis in cytostatic
chemotherapy (e.g. using GnRH analogues) has been attempted, but does not
provide sufficient gonadal protection
[38]. In radiotherapy, shielding of the
testes from radiation or removal from the
radiation field offers an effective measure to prevent unwanted damage and is
widely practiced.
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
277
Options for Fertility Preservation in Cancer Patients
Cryopreservation of Sperm
Cryopreservation of an ejaculate is the
established method of choice. Multiple
sperm donations can be provided and a
frozen depot created and maintained in
reproductive medical centers, prior to the
start of gonadotoxic treatment. This reserve could be used for ART-measures at
a later date. Spermatozoa are relatively
cryoresistant and post-thaw survival rate
is high. Many pregnancies have been
achieved using this method [39].
For prepubertal boys, cryopreservation
of sperm is inappropriate because provision of an ejaculate is not yet possible.
For adolescent boys undergoing puberty,
germ cells can be obtained for cryopreservation through extraction from testicular biopsies or by electroejaculation.
However, both methods are invasive procedures [40].
Cryopreservation of Sperm from
Testicular Tissue (TESE)
A testicular biopsy could be performed
to isolate spermatozoa from testicular
tissue when no spermatozoa are found in
the ejaculate. With this method, sperm
cells are present in up to 75% of cases.
TESE is an established process and is
combined with intracytoplasmic sperm
injection (ICSI) for later fertility. However, the success rate depends on the
amount of viable spermatozoa present in
testicular tissue at the time of cryopreservation [41].
The so-called Onco-TESE is particularly
useful in patients with unilateral or bilateral testicular tumors, as well as patients
with azoospermia before or after gonadotoxic therapy. Even for long-term
survivors of oncological diseases with
azoospermia, Onco-TESE can be offered
as an opportunity for future fatherhood
[42].
Experimental Approaches
Recovery of testicular tissue via biopsy
provides a method for recovery of germline stem cells before the start of treatment which can be maintained through
cryopreservation. This is currently the
only conceivable method to preserve fertility for prepubertal boys and, therefore,
the cryopreservation of immature testicular tissue should be considered for these
patients. After a successful treatment, the
tissue or the germ line stem cells contained therein could be used for process278
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
es which initiate the differentiation of
germ cells. The intact tissue could be
transplanted ectopically or orthotopically (autografts or ectopic xenografting).
Future studies should elucidate the most
appropriate method for clinical application [35].
 Conclusion
In view of the good treatment options
recently available for oncological diseases, it is now virtually essential to provide
patients of reproductive age with counselling regarding fertility preservation.
Fertility preservation is of great importance to many young women and men
diagnosed with cancer, and in general the
quality of counselling performance regarding fertility preservation is highly
valued by patients [43]. Today, there is a
large range of potential fertility preservation techniques available. For men,
sperm cryopreservation remains the gold
standard; by combination of cryopreservation with TESE/MESA or TESE/ICSI
there is a good chance to realize a desire
to have children. In women, transposition of the gonads before radiotherapy,
the use of GnRH analogues, and cryopreservation of embryos, oocytes and
ovarian tissue are available. The decision
as to which treatment is most suitable in
the patient’s individual situation has to
be made during a personal discussion
with her and requires intensive interdisciplinary communication, among oncologists, radiotherapists, and reproductive
medicine specialists. The individual approach is determined above all by the patient’s age, the nature of the tumor entity,
the remaining time before oncological
treatment, the planned treatment measures, and the urgency of the patient’s
wish to have children. Support and advice are available in German-speaking
countries from centers affiliated with the
FertiPROTEKT network, as well as from
the present authors. Details are available
on the network’s website,
www.fertiprotekt.eu
 Conflict of Interest
The authors certify that there is no conflict of interest with any financial organization regarding the material discussed
in the manuscript.
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Selected oral communication session at the ESHRE-meeting in
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279
From classical to molecular physiology
and back again
N. Einer-Jensen1, H. F. R. Hunter2
Combining classical organ physiology with cellular and molecular approaches would create a symbiosis. Local effects due to local counter-current transfer of
signal substances are underestimated. The authors have included suggestions for future experimental evaluation of these points.
This essay is an attempt to document the potential benefits if traditional organ physiological science is revitalised and combined with cellular and molecular physiology. This should create a symbiotic effect. Suggestions taken mainly from reproductive physiology are mentioned, as are possible benefits, not
least if applied in clinical situations. These include a) gamete and embryo culture systems with computerised control of specific temperature shifts, b) establishment of a very early pregnancy factor in women, c) using procedures of local counter-current brain cooling in hyperthermic emergencies, and d) applying
nasal or rectal counter-current physiology in therapeutic situations. J Reproduktionsmed Endokrinol 2014; 11 (5–6): 280–5.
Key words: counter-current transfer, hormones, blood vessels, local application, local effects
 Introduction
The authors are no longer young and
started working on experimental studies
in physiology soon after the unravelling
of DNA and invention of the electronic
library. In those days, physiology was
mainly in vivo and in vitro organ physiology, and research tried to describe the interaction between cells and organs [1].
During our careers, we have seen the development of cellular, biochemical and
molecular physiology. The new disciplines are certainly successful and have
produced dramatic results and major
steps forward, while traditional physiology has starved – it seems to be out of
fashion. Nonetheless, there has been development of modern electronic equipment, improved quality of experimental
animals and procedures of anaesthesia
etc., yet these are still not fully utilized.
Clinical pharmacology investigations financed by industry are common, while
basic clinical physiological research has
suffered. As a result, references in the
present article tend to be historic.
The paragraphs that follow concern
physiological integration between different organ systems, such as the importance of the cardio-vascular system for
organ function and organ interaction. It
is much more than a simple transfer of a
substance from A to B. Attempts will be
made to pin-point research results which
could not have been created in test tubes
alone. We will also suggest areas in need
of more information and further research
in domestic animals and humans. Most
examples are taken from reproductive
physiology since this is the research field
of the authors. Without doubt, comparable examples could be taken from other
areas.
The authors do not want to downgrade
the importance of any type of biochemical or molecular physiology research and
knowledge, but rather wish to strengthen
an understanding of the interactive aspects of physiology. Test tube physiology may be suitable to describe the function of an E. coli bacterium but it is insufficient to describe the function of a
mammalian organism. The suggestion is
to use the best of both worlds by reinvestigating classical physiology and combining it with the latest cellular and molecular techniques to obtain new knowledge. Such symbiotic studies represent a
way forward.
Young scientists perform literature
searches with a computer. One consequence of this approach is that scientific
activities and reports older than the rather recent computer age are overlooked or
reinvented. This fact of modern life
seems unavoidable. Young people never
do as told. Mature scientists may diminish the loss or damage by publishing review articles in good journals (e.g. [2,
3]). This will transfer old knowledge to
the present databases.
Evolution of mammalian organisms has
taken millions of years; the many special
arrangements so developed have a purpose. There are of course differences between species, but also many similar
mechanisms and likewise different
mechanisms to achieve the same physiological goal. In most aspects, man seems
to behave as a typical mammal. As a consequence, we may be able to answer
some parts of the following questions,
but further development of knowledge
should keep future generations of physiologists usefully occupied and intellectually stimulated.
 Integration between the
Circulatory System and
Organs of the Reproductive-Endocrine Systems
Humoral regulation is a transfer of regulatory substances from one cell (group of
cells or whole organs) to another system
of cells. “Regulatory substances” covers
a broad range of substances, including
traditional hormones, prostaglandins,
and regulatory peptides. Three types of
humoral distribution will be mentioned,
Received: June 10, 2014; accepted after revision: October 31, 2014
From the 1Molecular Medicine, University of Southern Denmark, Odense, Denmark, and the 2Institute for Reproductive Medicine, Hannover Veterinary University, Hannover, Germany
and Sidney Sussex College, University of Cambridge, Cambridge, U.K.
Correspondence: Niels Einer-Jensen, DVM, DScDVM, DScMD. Molecular Medicine, University of Southern Denmark, Langelinie 144, DK-5230 Odense M, Denmark;
e-mail: [email protected]
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Physiology, forward and back
the third point being the main topic of
this article:
1. Diffusion between neighbouring cells.
A signal substance may diffuse to an
adjacent cell through the extracellular fluid. This mode of action is
termed paracrine. The maximum distance is probably of the order of 10 µ,
otherwise the substance will diffuse
into a capillary and the potential local
effect will be abolished. Transmitter
substances in the nervous system
may be placed in this group as a special case with a closed diffusion
space.
2. There is a high density of capillaries
in every organ. The diffusion distance between a cell and a capillary is
minute. When locally produced molecules diffuse in the extracellular
space, they will, with a high probability, diffuse through a capillary wall
into the lumen and be carried away.
During the next passage of a capillary, such molecules may diffuse
through the wall and extracellular
space into a cell and perform an appropriate regulation. This mode of
action is endocrine and represents
traditional endocrinology.
3. Vessels to and from an organ, and
even within an organ, may be anatomically very close and form a
counter-current transfer system. This
offers a local redistribution system
that creates increased concentrations
of locally-produced substances in the
neighbouring artery compared with
the aortic concentration. This increased concentration may have a local effect on other cell groups in the
actual organ or in other organs supplied from the same local artery. This
mode of action could be called counter-current endocrine and is a common but frequently overlooked mechanism.
 Basic Rules underlying
Exchange from the Circulatory System to and
from Organs
The vascular system is not a passive set
of tubes. Rather, it is a highly developed,
dynamic, and exceedingly complicated
system, which influences the transfer of
substances and where many of the substances being transferred have an impact
on the function of the exchange system
itself.
Diffusion in and out of blood vessels is
mainly a passive process. Small molecules diffuse more effectively than larger
ones, but even substances with a molecular weight of 500 Daltons or more may
pass. Proteins will only pass to a minute
degree. Lipophilic substances diffuse
more effectively than hydrophilic substances of the same molecular weight. A
low blood velocity in capillaries will facilitate equilibrium of substances between extracellular fluid and plasma. Excess fluid in the extracellular space (oedema) will delay diffusion to and from
the capillaries and may disrupt normal
capillary flow; substances will not be
transferred properly.
Many substances are bound effectively
to plasma proteins (a single albumin and
diverse globulins); close to 100% binding is common. Only the non-bound
fraction is physiologically active. When
a hormone diffuses from the production
site into the venous blood, it is not protein-bound. It remains free in the blood
for a limited period (seconds) before becoming bound; an equilibrium was not
reached in bovine plasma even after
10 sec [4]. When a substance is transferred from venous to arterial blood
through the walls of the vessels, it arrives
unbound. If the binding takes just a few
seconds, the free hormone will reach the
capillaries before binding. A small percentage of unbound substance will therefore increase the total of free hormone
substantially whereas the increase in total concentration will be small. Locally
transferred hormones may thus have a
huge impact. Plasma binding kinetics
under in vivo conditions remains a critical but almost overlooked topic.
Total blood flow through an organ may
differ from the total capillary flow due to
the presence of shunts. Functional arterio-venous anastomoses doubling the total blood flow are present, for example,
in sheep ovaries without corpora lutea
[5]. The reason is not obvious.
Despite their low rate of flow, the lymphatic vessels are part of the local transfer system as the hormone concentrations are very high [6, 7].
 Questions Demonstrating
the Limitations of Knowledge in Physiological Science
Why is the Temperature of the
Testis and Epididymis lower
than Body Temperature?
It is basic physiological knowledge that
testicular temperature is 1–2°C or more
below deep body temperature in mammalian species with scrotal testes. The
cooler testicular venous blood is in close
contact with the artery in the Pampiniform plexus and cools the arterial blood
[8]. The heat transfer is close to 100% effective, thus keeping the heat loss needed
through the scrotum to a minimum [9].
The head of the epididymis is supplied
from the testicular artery and therefore
has a low temperature. The low temperature in scrotal mammals is thought to be
essential for sperm maturation, including
both nuclear and membranous changes,
and for functioning as a cool storage site
for sperm before ejaculation. These presumptions may be correct and indeed essential, but very large mammals like
whales and elephants have testes in the
abdomen. The reasons for a low temperature in scrotal mammals have not been
clarified, although a possible reduction
in the incidence of germ-line mutations
is frequently mentioned.
What is the Importance of
Intra-Testicular and TesticularEpididymal Signals?
One may postulate that cooling is just a
side effect of hormonal redistribution. It
is known that peptides and steroids are
transferred to the testicular arterial blood
in the Pampiniform plexus [10, 11].
Since the hormones are of testicular origin, they are recirculated to the testis and
epididymis, thus creating a higher tissue
concentration and essential effect locally. The increase in total hormonal content may be limited, but the hormones
add significantly to the non-protein
bound fraction for a brief period. Very
few experiments have taken this into account.
Local transfer of testosterone in primates
has been found by several groups of scientists [12, 13], but we still need information about changes in the testis induced by local hormone transfer. Local
peptides may be produced and transferred. They may be difficult to measure
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
281
Physiology, forward and back
in peripheral blood samples due to dilution, although it could be possible to
develop molecular probes to detect the
levels in local samples. This would be an
example of combining traditional physiology and molecular biology. Detection of peptides transferred via the local
vascular system would add to our understanding of the regulation of sperm development. A testosterone binding protein in rete testis fluid was once thought
to be essential for the transport of testosterone from testis to epididymis, but it
may be of less importance due to the
local vascular supply of the hormone.
It could be tempting to stimulate testicular or epidymal function through appropriate intramuscular testosterone injections. The peripheral testosterone concentration in blood may increase. However, the overall testicular production
would decrease due to decreased stimulation with gonadotrophins caused by
negative feedback from the peripheral
injection. In addition, the local influence
of counter-current transfer of testosterone could be abolished.
Why is the Temperature of
large Graafian Follicles lower
than in the rest of the Ovary?
The close apposition between the ovarian vessels in man was observed long ago
[14]. Such intimacy indicates a countercurrent mechanism, the presence of
which was confirmed more than 300
years later [15, 16]. Many animal experiments in several species have also documented counter-current transfer [17].
Large pre-ovulatory follicles may be one
or two degrees Centigrade cooler than
the rest of the ovarian tissues [18, 19].
Nature has developed a local cooling
system for pre-ovulatory follicles within
a complicated organ positioned deep in
the abdomen. The cooling may be important for the development process of
the gamete or for the follicular tissues,
but we do not know why or how. It is unlikely that evolution of such complicated
processes involving both male and female gametes does not have a purpose.
Fertility work involving follicle or oocyte culture could be performed at an appropriate reduced temperature although,
in reality, subtle changes in temperature
may be required. A computerized temperature control program should provide
a way forward in this dynamic sphere.
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Cooling of the large follicles may be a
“side effect”, since all known vascular
networks exchanging heat energy also
transfer substances. Such local transfer
of regulatory substances may create a
not-yet-investigated local environment.
This is an area where traditional animal
experiments and molecular physiology
together may clarify a long-standing conundrum.
What is the Significance of
Intra-Ovarian Signals?
The adult ovary is an organ with diverse
tissue types (follicles, corpora lutea, corpora albicantia, interstitial cells) and a
cyclic function. Small follicles grow to
medium size and some of them are stimulated to become mature, others to degenerate. Follicular growth is influenced
by larger follicles and corpora lutea.
There is every reason to believe that
much of the ovarian regulation is local
through local diffusion between neighbouring cells or through exchange between the ovarian vein and arterial blood
of steroids and peptides. Mid-size follicles may be stimulated or inhibited by
hormones from one or several large follicles. Local recirculation of progesterone from one or multiple corpora lutea
may also regulate follicular growth. The
fine-tuning of stimulation versus degeneration as well as the selection of the
large “successful” follicles are not fully
understood. Ovulations tend to shift between the ovaries in species with a single
ovulation (the shift is not obligatory) but
the tendency to alternation indicates that
a one-sided regulation is involved. The
field is open for investigation. In this
context, a regulatory influence of germ
cells should not be overlooked. Indeed,
one of the authors has proposed that the
oocyte acts as a centrally-located computer, programming and integrating conversations with ovarian somatic cells
[20].
What is the Importance of Local
Signals from the Ovary to the
Fallopian Tube and Uterus?
The Fallopian tube receives the eggs and
sperm, and fertilization occurs here. The
young embryo(s) are maintained in the
tube for some days (2–7 days), depending on species. The tube is a highly developed organ, much more than a simple
conduit. Sperm transport and control of
their numbers in the Fallopian tube are
tightly regulated processes, as is move-
ment of the fertilized eggs (embryos)
stepwise through the tube. Nutrition of a
developing embryo is made available
through secretory processes in the tube.
Immunological suppression may occur
since the embryos contain foreign proteins from the male genes. Signals derived from the ovary prepare the tube for
a developing embryo [21, 22]. A branch
of the ovarian artery supplies the Fallopian tube. Ovarian hormonal signals transferred in the vascular plexus will reach
the tube locally. In mono-ovulatory animals and man, progesterone and oestrogens will reach the ipsilateral tube in
“higher than normal” concentrations due
to local transfer. Since the function of the
tube is hormone-dependent, a local impact must be expected – and the hormonal changes are not measurable in peripheral blood. The morphology and function
of the Fallopian tube on the ovulatory
and contralateral sides should be compared during the ovulatory cycle in man.
Any difference between the two tubes
would strongly support ipsilateral mechanisms. It is improbable that progesterone and oestrogens are the only regulatory substances. Signal peptides may be
expected as well as prostaglandins. Here
again is a rich field for investigation
combining in vivo trials with molecular
techniques.
The ipsilateral aspect is documented in
man [23, 24]. During the follicular and
luteal phases, the border from either the
uterine or ovarian arterial supply is moving in the ipsilateral side of blood supply
during each ovulatory cycle. The ovulatory side is “preparing” the utero-tubal
junctional region to receive the developing embryo through oestrogen secretion
and later through progesterone secretion,
both hormones being transferred unilaterally to the ovarian and thus tubal arterial blood. Observations suggest that
miscarriage is less likely if the embryo
implants in the ipsilateral fundus, again
supporting the unilateral aspect. It is surprising that assisted fertility work is as
successful as it is when considering our
limited knowledge of early events in the
primate uterus.
What is the Purpose of Local
Signals from the Fallopian
Tube and Uterus to the Ovary?
The ovarian veins drain the ovary and
Fallopian tube and also parts of the uterus. Uterine blood supply may be an im-
Physiology, forward and back
portant factor in the regulation of the
oestrous cycle [25]. This is a region in
which arterial supply and venous return
are not identical. In cows, sheep and
several other species, PGF2 is secreted
from the uterus late in the oestrous cycle
if fertilization fails or if eggs are retained
in the Fallopian tube or embryos fail to
implant – this is a non-pregnant signal
inducing degeneration of the corpus luteum. Counter-current transfer of prostaglandin takes place in the ovarian veinarterial plexus, the concentration in peripheral blood being hardly measurable
due to metabolism of the hormone during the first pulmonary passage [26]. The
same mechanism is not present in man,
where a positive pregnancy stimulus
(hCG, human Chorionic Gonadotrophin)
is the accepted means of maintaining
corpus luteum function. hCG is measurable in peripheral blood a week after
conception, and commercially available
urine assay kits will confirm conception
after a missed menstrual period. hCG is
probably too large a molecule to be
transferred in the vascular plexus and an
active transfer mechanism has so far not
been documented. There is some indication that degeneration of the corpus luteum is prevented before the hCG level is
significantly increased.
Hormone-containing intra-uterine devices (IUDs) are documented to be effective
in preventing pregnancies, whilst at the
same time diminishing side effects of
IUDs such as spotting and menstrual
bleeding volume. Observations indicate
that they also have an effect on ovarian
function (which could involve local
transfer mechanisms).
Concerning signals from the uterus to
the ovaries, there remain outstanding
questions. For example, at the end of the
luteal phase in pigs, there is controversy
as to the mechanism of establishing
pregnancy. In the presence of embryos,
the uterine luteolysin PGF2 is said to
be internalised into the uterine lumen
(exocrine secretion) rather than entering
the uterine veins [27]. However, results
from another laboratory using the pig
model show that high titres of PGF2
can indeed enter the uterine veins at the
time of establishment of pregnancy
(Days 13–16). The explanation proposed here was that luteotrophins from
the many elongated conceptuses overcome the influence of uterine luteolysin
and permit establishment of the corpora
lutea of pregnancy [28]. Further studies
are needed to reconcile these differences. A potent local impact of multiple viable conceptuses should not be overlooked.
How soon does a Woman
know she is Pregnant?
Many years ago, an Australian group
postulated the presence of an “early
pregnancy factor” (EPF) in serum [29].
The work was controversial because, in
the beginning, it was difficult to repeat
the Rosette test in other laboratories.
Nonetheless, later immunological investigations supported the idea. The putative
factor was found in pregnant women
[30]. This, together with the suspicion
that hCG may on occasions be produced
a few days too late to promote survival of
the corpus luteum, make more work
around EPF much needed. The present
authors postulate that the young embryo
secretes a “pregnancy signal” in minute
concentrations which is amplified by the
neighbouring suspension of follicular
cells [31]. The signal is detected by the
endosalpinx and induces a larger production of the “real” early pregnancy signal.
Molecular biology should be applied in
suitable animal experiments to test this
hypothesis. The EPF may, especially
during the first days of a pregnancy, be
difficult to measure in peripheral blood
due to dilution. It may also be difficult to
investigate the topic in man for ethical
reasons, but it is potentially of considerable importance and could be performed
using in vitro culture material.
Only 15–30% of the implanted embryos
survive to give viable foetuses. This estimate is based on the assumption that
most delayed menstruations are associated with early abortions. Vaginal progesterone treatment following egg transfer
seems to increase the pregnancy rate to
the normal range, but treatment with
EPF, if it ever becomes available, may
improve the outcome. Women sometimes describe “being sure” of their pregnancy a few days after conception, but a
clinical trial around the issue is missing.
A key trial could involve weekly blood
samples from “just married women”
lacking any contraception. hCG, EFP,
and progesterone concentrations should
be correlated with the subjective experiences of the women (when did you feel
pregnant?).
Why is the Adrenal Gland Producing both Adrenalin and
Corticosteroids?
The adrenal gland is a morphologically
unusual combination: the cortex producing corticosteroids develops from mesoderm and the adrenalin producing medulla originates from ectoderm, combination of distinct tissues also exists in the
pituitary gland. A probable explanation
for this arrangement is that adrenalin
producing tissues benefit from the close
contact with the corticoid producing tissue [32]. It has been suggested that local
transfer of corticoids from the small
veins to the adrenal artery takes place
and facilitates adrenalin production.
Medication with corticoids will suppress
the cortical production of hormones and
this may influence adrenalin production.
This possibility appears not to have been
been investigated with modern techniques.
What is the Purpose of a Cooling Mechanism to the Brain?
The survival of a mammal is threatened
if the body temperature increases by 5°
or 6° C; the first organ to be damaged is
the brain. Running (fight or escape), fever and environmental heat stress may
thus be life-threatening. A brain cooling
mechanism has been documented in ruminants including camels, likewise in
pigs and rats [33]. A cooling mechanism
has also been postulated in the horse and
man. Respiratory air cools the nasal cavity and therefore the nasal venous blood.
Heat energy is exchanged between this
blood and carotid blood in the plexus,
decreasing the temperature by several
degrees Centigrade in carotid blood. Increased respiration due to running or
heat stress will increase the cooling effect. Auto-regulation prevents cooling if
the brain temperature is normal or low;
the blood will be redirected from the
deep veins to superficial veins before
reaching the jugular veins.
The mechanism has not been fully documented in man. In clinical studies, pressure and temperature probes are used in
hypothermic patients, but the brain cooling thesis cannot be tested in this group
of patients as the cooling mechanism is
shut down in the hypothermic patient by
an auto-regulatory mechanism. Weis et
al. [34] have suggested a new method for
temperature measurements in man based
on Magnetic Resonance Spectroscopy
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
283
Physiology, forward and back
Imaging (MRSI). We suggest a pre-hospital investigation on intubated, potential
or actual hyperthermic patients: flush the
nasal cavity in intubated patients with air
or oxygen before arrival at the hospital.
One logical consequence is that brain
damage should be less extensive.
Does a Local Hormonal Exchange System exist in the
Brain?
The short answer is “yes”. Steroid transfer from nasal vein blood or the nasal
cavity has been demonstrated in isolated,
perfused pig heads [35]. Transfer of several substances has also been found from
the nasal cavity in rats [36]. It should be
possible to treat patients by way of nasal
application to obtain higher brain arterial
concentrations than indicated by peripheral blood samples; one may call it a favourable therapeutic ratio. The topic is
under-explored, and human trials and
better animal models are needed. The
clinical possibilities are considerable.
Has the brain vascular transfer system
developed to favour brain cooling or for
signal substance transfer or both? Why
have comparable transfer mechanisms of
hormones evolved in the brain, the testis
and the ovary? The physiological advantages must be significant. Could molecular studies give guidance here? Regulation of temperature is critical for nuclear,
cytoplasmic and membrane function.
Are hormones distributed by
the Peritoneal Fluid?
The peritoneal cavity is not passive, and
its ability to combat infections is well
known. However, the possible involvement of the peritoneum in distribution of
hormones is seldom appreciated [37].
Man is predominately mono-ovulatory.
In each cycle, the ovary producing the
dominant follicle and corpus luteum creates a unilateral hormonal sphere influencing the function of the nearby organs
(Fallopian tube, tip of uterus) [38]. The
local hormonal environment is mainly
created by local transfer of hormones between the blood and lymph vessels, and
also by post-ovulatory leakage from the
ruptured follicles which have elevated
steroid concentrations in the coagulated
follicular fluid. Local concentration differences in steroid hormones have been
found in peritoneal fluid, and peritoneal
fluid is in contact with the endosalpinx.
Pre-ovulatory oestrogens and post-ovu284
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
latory progesterone in peritoneal fluid
may influence diverse functions of the
Fallopian tube. Peritoneal fluid may
therefore prove part of the explanation
for a local regulation.
Hormones in peritoneal fluid may include not only those derived from the
ovaries, but also from the intestines, its
mesenteries and associated deposits of
adipose tissue such as leptin. In this regard, post-operative surgical adhesions
developing between the uterus and intestines in pigs induce maintenance of the
corpora lutea, an observation corroborated by suturing together 15–20 cm portions of corresponding uterine and intestine tissues [Léglise PC, Hunter RHF,
1968, unpublished observations].
Why is Drug Administration via
the Nose, Oral Cavity, Rectum,
and Vagina not yet universally
accepted when enhanced local
Effects can result from such
Treatment?
The short answer is: lack of knowledge
and little discussion in the medical
school curriculum.
There are many advantages in these special routes of administration. However,
interest in such routes is limited and few
investigations have been made. There
may even be a built-in negative bias: patients and doctors do not like it, it is a
nuisance; both groups want oral pills or
injections. Rectal or vaginal treatment
used to be quite common but it gradually
went out of fashion. This was before the
distinct benefits of local drug administration were documented. Doctors and
veterinarians introduced long-acting antibiotics and sulphur pills, oil suspension
or implants into the uterus or rectum.
The dose was smaller than for general
treatment (penicillin was expensive in
those days) and, especially in ruminants,
the effect on the stomach microflora was
less dramatic. Few treatments survived:
progesterone (gestagen) containing “vagitories”, the treatment seemed successful in preventing early abortions after
embryo transplantation; and sublingual
application of nitroglycerine against angina pectoris. Vaginal application of oestrogens may also be useful to treat incontinence, since local transfer of substances takes place from the vagina to the
uterus and bladder. The underlying rationale is that the first-pass liver metabo-
lism is avoided and a local favourable
therapeutic ratio induced.
Counter-current transfer mechanisms
add a new argument for local treatment,
and the following comments will indicate the possibilities:
1. Intubated individuals with a high
body or brain temperature should anticipate less brain damage if air is
blown into the nasal cavities to cool
the brain arterial blood. Clearly, this
will not work at low body temperatures, but it does offer a safe and easily applied pre-hospital tool.
2. Drugs in nasal sprays may be locally
transferred to brain arterial blood,
and this partly specific treatment
would favour the CNS compared to
the peripheral nervous system. The
system works in some animal species
and possibly also in man. The documentation remains weak and further
studies would be valuable.
3. Oral deposition of drugs has a special
use at present: nitroglycerine under
the tongue to enhance cardiac circulation. This is a proven quick and effective treatment – one may think of
other possibilities.
4. Rectal administration has also a proven history, but patients tend to dislike
the method. A first pass of the liver is
avoided. The vascular supply to the
distal 5–10 cm of rectum indicates
that local transfer to the uterus and
bladder may take place. In gynaecological cases, the rectum may be as
useful in this respect as the vagina. In
the male, rectal administration could
be used for local treatment of bladder
and prostate problems, but systematic investigations are needed.
5. Vaginal administration may be useful
under specific circumstances. At
present it is the most widely used application exploiting the advantages of
a local counter-current transfer system. It is probably often used without
knowledge of the local transfer. Vaginal administration of small doses of
oestrogens (pills glued to the vaginal
wall) tends to diminish incontinence
in mid-aged women. Administration
of progesterone after embryo transfer
seems effective in preventing early
abortion. Vaginal introduction of
prostaglandin is used after administration of anti-gestagens in early
pregnancy to induce uterine contractions and abortion.
Physiology, forward and back
 Conclusion
8. Morgentaler A, Stahl BC, Yin Y. Testis and temperature: an
historical, clinical, and research perspective. J Androl 1999; 20:
189–95.
The authors believe that studies combining classical organ physiology with cellular and molecular approaches would
create a symbiosis that should increase
our present knowledge dramatically.
Furthermore, we believe that local effects due to local counter-current transfer
of signal substances are underestimated
and should always be included when discussing regulation of any organ function.
The authors have included various suggestions for future experimental evaluation of these points.
9. Sørensen HG, Lambrechtsen J, Einer-Jensen N. Efficiency of
the counter current transfer of heat and 133xenon between the
pampiniform plexus and testicular artery of the bull under in
vitro conditions. Int J Androl 1991; 14: 232–40.
 Conflicts of Interest
14. De Graaf R. De Mulierum Organis Generationi Inservientibus
Tractatus Novus. Hack, Leyden, 1672.
Both authors contributed to the manuscript. Neither has any conflicts of interest.
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Top Mol Endocrinology 1975; 2: 181–94.
11. Bayard F, Boulard PY, Huc A, Pontonnier F. Arterio-venous
transfer of testosterone in the spermatic cord of man. J Clin
Endocrinol Metab 1975; 40: 345–6.
12. Dierschke DJ, Walsh SW, Mapletoft RJ, Robinson JA,
Ginther OJ. Functional anatomy of the testicular vascular pedicle in the rhesus monkey: evidence for a local testosterone concentrating mechanism. Proc Soc Exp Biol Med 1975; 148: 236–
42.
13. Einer-Jensen N, Waites GM. Testicular blood flow and a
study of the testicular venous to arterial transfer of radioactive
krypton and testosterone in the rhesus monkey. J Physiol 1977;
267: 1–15.
15. Bendz A, Einer-Jensen N, Lundgren O, Janson PO. Exchange
of krypton-85 between the blood vessels of the human uterine
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285
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Einladung
zum 6. Praxisseminar der AGRBM
17. – 19. April 2015
in Düsseldorf
Liebe Kolleginnen und Kollegen,
wir möchten Sie und Euch ganz herzlich zum 6. Praxisseminar der AGRBM nach Düsseldorf einladen. Vom 17. bis 19. April 2015 bietet sich uns die Möglichkeit, in bewährter Form Erfahrungen
und Meinungen auszutauschen und neue Ideen für die tägliche Arbeit zu sammeln.
Neben einem grundlagenwissenschaftlichen Block zur Physiologie der regelrechten und fehlerhaften Implantation möchten wir einen Blick über den Tellerrand des Laboralltags wagen und
uns einem Themenblock widmen, der in vielen Zentren immer mehr Raum einnimmt. Traditionelle chinesische Medizin, Hypnose und die psychosomatische Begleitung des Kinderwunschpaares – alles Hokuspokus oder wichtiger Bestandteil einer ganzheitlichen Behandlung?
Die Seminarthemen spiegeln die vielen Facetten der Reproduktionsbiologie wider. Eine Neuerung ist die Verlängerung des Seminarteiles auf zwei Blöcke, so dass die Möglichkeit besteht,
zwei Seminare zu besuchen.
Die Abendveranstaltung wird Düsseldorf von seiner schönsten Seite zeigen – vom Rhein aus –
beste Voraussetzungen für einen stimmungsvollen Abend!
Abgerundet wird unser Treffen durch die traditionelle Diskussionsrunde am Sonntagvormittag,
zudem wird die Industrie ihre Produkte im Bereich Labormonitoring vorstellen. In Zeiten immer
schwieriger werdenden Sponsorings, sind wir froh, auch dieses Jahr wieder viele Industrievertreter begrüßen zu dürfen.
Wir freuen uns sehr auf das gemeinsame Treffen – wir heißen altbekannte und neue Gesichter
willkommen in Düsseldorf!
Herzliche Grüße aus dem Rheinland
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6. Praxisseminar der AGRBM
17. – 19. April 2015 in Düsseldorf
Programm
Freitag,
17. April 2015
13.30 – 15.00 Uhr
1. Seminarteil
ab 15.00 Uhr
Anmeldung
Andrologie: Strategien der Spermienaufarbeitung oder
– Vernachlässigen wir die Männer?
Hans-Christian Schuppe (Gießen), Verena Nordhoff
17.00 – 19.00 Uhr
Hauptversammlung der AGRBM
19.30 Uhr
Come-together mit Live-Cooking
Forum Junge Biologen: Was ich noch nie gefragt habe,
aber immer schon wissen wollte!
Dunja Baston-Büst, Ralf Böhm
Ohne Kommunikation ist alles nichts?
Dagmar Nitsch-Musikant (Marl)
Samstag,
18. April 2015
15.00 – 15.30 Uhr
Kaffeepause /Ausstellungsbesuch
ab 8.00 Uhr
Anmeldung
15.30 – 17.00 Uhr
2. Seminarteil
8.45 Uhr
Begrüßung
Andrologie: Strategien der Spermienaufarbeitung oder
– Vernachlässigen wir die Männer?
Hans-Christian Schuppe (Gießen), Verena Nordhoff
Vorträge
9.00 Uhr
Immunologie der Implantation
Sabine Seegerer (Hamburg)
9.30 Uhr
Eileiter-Physiologie und EU
Andrew Horne (Edinburgh)
10.00 – 10.30 Uhr
Kaffeepause /Ausstellungsbesuch
10.30 Uhr
TCM und IVF: Möglichkeiten und Grenzen
Tanja Emde (Düsseldorf)
11.00 Uhr
Psychosomatische Aspekte der
Kinderwunschbehandlung
Andrea Schäfer (Düsseldorf), Silke Gervers (Neuss)
11.45 Uhr
Hypnose und IVF: alles nur Zauberei?
Kirsten Voigt (Köln)
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PKD und PID: Anwenderforum
Werner Hoppenstedt, Jens Hirchenhain, NN
Ohne Kommunikation ist alles nichts?
Dagmar Nitsch-Musikant (Marl)
18.45 Uhr
Abfahrt der Busse
19.00 Uhr
Festabend:
„Eine Schifffahrt, die ist lustig…“
Sonntag,
19. April 2015
9.00 – 10.30 Uhr
Firmenpräsentationen zum Thema „Labormonitoring“
10.30 – 11.00 Uhr
Zusammenfassung der Seminare von Samstag
11.00 – 12.30 Uhr
Offene Diskussionsrunde
12.30 Uhr
Veranstaltungsende
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www.agrbm.de / www.repromedizin.de
Mitteilungen der Gesellschaften – AGRBM und DGRM
PROGRAMM
Gesellschaftsmitteilungen
9.00 Uhr
Begrüßung
9.15 – 10.45 Uhr
Dr. Alberto Tejera, PhD
Clinical application of time lapse embryoculture
– the IVI experience
+
Dr. med. Ines Beyer
Endometriose & Fertilität – Aktuelle Aspekte aus Klinik
und Forschung
10.45 – 11.15 Uhr
Kaffeepause
Liebe Kolleginnen und Kollegen,
wir möchten Sie sehr herzlich zur ersten gemeinsamen
Fortbildungsveranstaltung von AGRBM und DGRM nach
Düsseldorf einladen. Reproduktionsmedizin und Reproduktionsbiologie – zwei spannende Fachgebiete, die zusammen gehören! Das Konzept der Veranstaltung zielt ganz
bewusst darauf ab, beide Gebiete zu verzahnen. Die Teilnehmer können dabei sowohl Bekanntes vertiefen als auch
neue Einblicke gewinnen. Das Programm bietet hochklassige Experten aus Forschung, Labor, Klinik und Recht
– ein weiter Bogen, der viele Aspekte unseres breit gefächerten Feldes beleuchtet. Wir freuen uns darauf, viele von
Ihnen in Düsseldorf zu begrüßen!
11.15 – 12.45 Uhr
Prof. Carlos Simon, MD, PhD
Genetic matching of oocyte donor and recipient couple:
what is possible, what is reasonable?
+
Prof. Dr. jur. Helmut Frister
Embryonenschutzgesetz und PID – wo stehen wir aktuell
in Deutschland?
12.45 – 13.30 Uhr
Mittagspause
Herzliche Grüße
13.30 – 15.45 Uhr
Dr. Ana Cobo, PhD
Slow-freezing or vitrification of human gametes and
embryos in daily IVF-routine – one protocol for everything?
+
PD Dr. med. Ariane Germeyer
Kryokonservierung und Retransplantation von
Ovargewebe – Erfahrungen aus dem Netzwerk Fertiprotekt
+
PD Dr. med. Sören von Otte
Social Freezing – eine „dauerhaft junge“ Versicherung?
Jan-Steffen Krüssel + Jens Hirchenhain + Dunja Baston-Büst
Verabschiedung
ORGANISATION
Prof. Dr. med. Jan-Steffen Krüssel
Dr. rer. nat. Jens Hirchenhain
Dr. rer. nat. Dunja Baston-Büst
Universitätsfrauenklinik Düsseldorf
Universitäres interdisziplinäres
Kinderwunschzentrum Düsseldorf (UniKiD)
Moorenstr. 5, 40225 Düsseldorf
17.
JANUAR
2015
DÜSSELDORF
VERANSTALTUNGSORT
Haus der Universität
Schadowplatz 14, 40212 Düsseldorf
www.hdu.hhu.de
WWW.
AGRBM.DE
WWW.
DGRM.EU
INFORMATION + ANMELDUNG
DGRM Geschäftsstelle
Amsterdamer Weg 78, 44269 Dortmund
Telefon 0231-909 80 23, Mobil 0173-238 57 73
Fax 0231-906 24 51
[email protected]
www.agrbm.de
www.dgrm.eu
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
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Mitteilungen der Gesellschaften – BRZ
www.repromed.de
Gesellschaftsmitteilungen
BRZ-Mitteilungen
Ankündigung
Der BRZ freut sich außerordentlich darüber, dass die nachstehend genannte Studie nun endlich veröffentlicht werden kann.
Als Mitglieder des Wissenschaftlichen Beirats haben Herr Professor H. Kentenich und Herr Dr. A. Jantke (BRZ) das „Werden“
der Studie inhaltlich begleitet.
 Untersuchung zur Situation von ungewollt und gewollt kinderlosen Frauen
und Männer in Deutschland
Im Auftrag des Bundesministeriums für Familie, Senioren,
Frauen und Jugend wurde eine sozialwissenschaftliche Untersuchung zur Situation kinderloser Frauen und Männer in
Deutschland vom DELTA-Institut für Sozial- und Ökologieforschung durchgeführt. Ziel war es, die Kinderlosigkeit von
Menschen aus unterschiedlichen Milieus sowie deren Ursachen und Folgen unter den besonderen Aspekten Geschlecht,
Alter, Lebensphase, Lebenslauf, Werteorientierung, Lebensstile, Partnerschaft, soziales Umfeld und Migrationshintergrund zu erforschen.
Die jetzt vorliegenden milieuspezifischen Untersuchungsergebnisse liefern erstmals valide Daten und Befunde über die
vielfältigen Gründe, Motive, Auswirkungen und auch Diskriminierungserfahrungen kinderloser Frauen, Männer und Paare. Die sich daraus ergebenden zielgruppendifferenzierten
Erkenntnisse sollen als Grundlage für Maßnahmen zur früh-
zeitigen Aufklärung über (In-) Fertilität, zur Stärkung der
psychosozialen Kinderwunschberatung und zur Verbesserung der gesellschaftlichen Akzeptanz bei Inanspruchnahme
reproduktionsmedizinischer Behandlungen dienen.
Insgesamt wird dies dazu beitragen, das Thema Kinderlosigkeit zu enttabuisieren und die Stigmatisierung der betroffenen Paare zu vermindern.
Die Veröffentlichung der wissenschaftlichen Untersuchung
soll noch in diesem Jahr erfolgen.
Weitere Informationen hierzu finden Sie unter
http://www.informationsportal-kinderwunsch.de/node/283.
Korrespondenzadresse:
Bundesministerium für Familie, Senioren, Frauen und Jugend
Fachreferat 414
Tel.: 030/20655-0
E-Mail: [email protected]
Ordentliche Mitgliederversammlung des BRZ 2015
Freitag, 1. bis Sonntag, 3. Mai 2015
in Berlin – gleiche Stelle – gleiche Welle, im Abion Hotel Spreebogen.
290
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
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Str.
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hrb
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ter
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irc
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hS
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Circus
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alle
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www.dgandrologie.de
Mitteilungen der Gesellschaften – DGA
Gesellschaftsmitteilungen
DGA-Mitteilungen
ϭϰƚŚ ƚŽ ϭϲƚŚ ŽĨ &ĞďƌƵĂƌLJϮϬϭϱ
&ĂĐƚŽƌLJ,ŽƚĞůͲ DƺŶƐƚĞƌͲ 'ĞƌŵĂŶLJ
ys/ƚŚ /ŶƚĞƌŶĂƚŝŽŶĂůtŽƌŬƐŚŽƉŽŶƚŚĞ
ĞǀĞůŽƉŵĞŶƚĂŶĚ &ƵŶĐƚŝŽŶ ŽĨ ƚŚĞ ZĞƉƌŽĚƵĐƚŝǀĞ KƌŐĂŶƐ
'ĞƌŵůŝŶĞ ^ƚĞŵĐĞůůƐĂŶĚWƌŽŐĞŶŝƚŽƌƐ͗dŚĞZĞŐĞŶĞƌĂƚŝǀĞWŽƚĞŶƚŝĂůŽĨƚŚĞ'ŽŶĂĚƐ
^ƉĞĂŬĞƌƐ
ĂǀŝĚůďĞƌƚŝŶŝ͕h^
ƌĞnj ZĂnj͕'ĞƌŵĂŶLJ
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ZĞŶĞĞZĞŝũŽWĞƌĂ͕h^
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ZŽůĨ:ĞƐƐďĞƌŐĞƌ͕'ĞƌŵĂŶLJ
ǀĞůLJŶdĞůĨĞƌ͕hŶŝƚĞĚ<ŝŶŐĚŽŵ
WĞƚĞƌ<ŽŽƉŵĂŶ͕ƵƐƚƌĂůŝĂ
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ƌŽƌ DĞŝƌŽǁ͕/ƐƌĂĞů
ŶƐ ǀĂŶWĞůƚ͕ EĞƚŚĞƌůĂŶĚƐ
^ƚĞǀĞŶZĂŵŵ͕'ĞƌŵĂŶLJ
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dŚĞŶƵŵďĞƌŽĨƉĂƌƚŝĐŝƉĂŶƚƐŝƐůŝŵŝƚĞĚ͘&ŽƌĨƵƌƚŚĞƌŝŶĨŽƌŵĂƚŝŽŶƐĞĞŚƚƚƉ͗ͬͬǁǁǁ͘ƌĞƉƌŽǁŽƌŬƐŚŽƉϮϬϭϱ͘ĚĞ
WK͗DŝĐŚĞůĞŽŝĂŶŝ͕ǀĞůLJŶdĞůĨĞƌ͕^ƚĞĨĂŶ^ĐŚůĂƚƚ ĂŶĚ:ŽĂĐŚŝŵtŝƐƚƵďĂ >K͗:ŽĂĐŚŝŵƐƐĞůŵĂŶ͕,ĞůŽŝƐĂ >ĂǀŽƌĂƚŽ ĂŶĚhƌƐƵůĂZƺƐĐŚŚŽĨĨ
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
295
Gesellschaftsmitteilungen
Mitteilungen der Gesellschaften – DGA
www.dgandrologie.de
Andrologie
in der Praxis
Programm
Testosterongabe bei älteren ko-morbiden Patienten?
Prof. Hermann Behre / Halle
Praktisches Vorgehen bei Pubertätsstörungen
Dr. med. Julia Rohayem / Münster
Münster
27. und 28. Februar 2015
Der depressive andrologische Patient
Prof. Michael Zitzmann / Münster
Praktische genetische Beratung in der Andrologie
PD Dr. Frank Tüttelmann / Münster
Der andrologische Patient mit Varikozele
– praktisches Vorgehen
Dr. med. Karen Czeloth / Münster
Fertilitätsprotektion bei Jungen - wo stehen wir?
Prof. Stefan Schlatt / Münster
Erektile Dysfunktion – neue Therapieoptionen
Prof. Dr. med. Hermann van Ahlen / Osnabrück
Testosteronersatztherapie bei prostatektomierten Patienten
Prof. Dr. med. Herbert Sperling / Mönchengladbach
Operative Spermiengewinnung
Prof. Dr. med. Sabine Kliesch / Münster
Wie kann der Androloge mit dem Gynäkologen zusammen
arbeiten?
PD Dr. med. Andreas Schüring / Münster
Psychosomatische Störungen bei Männern
Prof. Dr. med. Gudrun Schneider / Münster
Tagungsort
Hands on Workshops
Factory Hotel
An der Germania Brauerei 5
48159 Münster
US Sessions
US Schilddrüse / Gefäß-Doppler
Spermiogrammkurs / KRYO
Tagungsleitung
Prof. Michael Zitzmann
Prof. Sabine Kliesch
Priv.-Doz. Dr. Frank Tüttelmann
Prof. Stefan Schlatt
296
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
Anmeldung
WICARA Kongressorganisation
Gabriele Wickert & José Aranzabal
Amsterdamer Weg 78 / 44269 Dortmund
Telefon: 0231-909 80 23 / Fax: 0231-906 24 51
Mobil: 0173-238 57 73
[email protected]
www.wicara.de
Weitere Informationen
www.dga-intensivkurs.de
Medizintechnik
InControl – unabhängige
Kontrolle im Labor
Qualität und Zertifizierung
Labotect fertigt Qualitätsprodukte und
ist bereits seit 2003 als einer der ersten
Medizinprodukte-Hersteller in Deutschland gemäß der DIN EN ISO 13485 kontinuierlich für Entwicklung, Produktion,
Vertrieb und Service für Geräte und Instrumente für die assistierte Reproduktion, Gynäkologie, Chirurgie und Gewebekultur zertifiziert. Bitte fragen Sie vor
Ihrer Kaufentscheidung immer nach den
Zertifikaten, deren Geltungsbereich und
überprüfen Sie im Zweifelsfall auch die
Benannte Stelle!
Labotect Labor-Technik-Göttingen GmbH
entwickelt, produziert und vertreibt eine
große Auswahl an Produkten für den
Einsatz im Bereich assistierte Reproduktion, in der Medizin und in naturwissenschaftlichen Laboren. Herausragende
Qualität und enger Kundenkontakt bestimmen die Firmenphilosophie seit über
40 Jahren. Inkubationstechnik ist einer
der Schwerpunkte von Labotect. Äußerst
kurze Erholzeiten für alle regulierbaren
Parameter bei einem sehr hohen Sicherheitsstandard sowie komfortablem Design sind grundlegende Eigenschaften
aller Labotect-CO2-Inkubatoren.
Das InControl 1050 wurde für die Kontrolle der Bedingungen in Inkubatoren
entwickelt, um Ihnen die Prüfung und
Auswertung von CO2, Temperatur und
O2 präzise und benutzerfreundlich zu ermöglichen.
Praktisch, zuverlässig und präzise:
InControl 1050 von Labotect
Das InControl 1050 erfasst präzise die
Messwerte von CO2, Temperatur und optional auch O2. Die CO2-Messung erfolgt
über einen Zweistrahl-Infrarot-Sensor,
welcher unabhängig von Temperatur und
Feuchte arbeitet. Die Dokumentation der
Werte kann als Einzelmessung oder in
Messreihen mit wählbaren Intervallen
Abbildung 1: InControl 1050
erfolgen, wobei die gemessenen Werte
mit Datum, Zeit und Inkubatornummer
gespeichert werden. Um Ihnen die Logistik in Ihrem Labor zu erleichtern, besitzt das InControl die Möglichkeit, die
Messwerte von bis zu 16 Inkubatoren zu
dokumentieren. Eine benutzerfreundliche Menüführung und die Möglichkeit,
die Daten direkt mittels USB herunterzuladen, runden das System ab. Der Betrieb ist mittels wieder aufladbaren LiIon-Batterien oder einem Steckernetzteil
möglich.
Vertiefende Informationen zum Thema
Zertifizierung und zu unseren Produkten
erhalten Sie gerne auf Anfrage. Erhalten
Sie einen Einblick in unser Produktsortiment und unsere Unternehmenskultur
und besuchen Sie unseren Internetauftritt
unter www.labotect.com!
Weitere Informationen und verantwortlich für den Inhalt:
Labotect GmbH
Postfach 200212
D-37087 Göttingen
E-Mail: [email protected]
www.labotect.com
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
297
Medizintechnik
Neueste Studienergebnisse belegen die Vorteile des
EmbryoScope™ für die klinische Praxis
Das EmbryoScope™ Time-Lapse-System (Abb. 1) ist seit 2009 im klinischen
Einsatz. Inzwischen wurden Embryonen
von über 200.000 Patientinnen mit dem
EmbryoScope™ behandelt. Gewonnene
Erfahrungen haben Hinweise geliefert,
dass das EmbryoScope™ Time-LapseSystem in der klinischen Anwendung
entscheidende Vorteile bietet. Eine neue,
multizentrische Studie aus Spanien belegt nun eindrucksvoll, dass das EmbryoScope™ herkömmlichen Kulturmethoden überlegen ist.
Abbildung 1: EmbryoScope™ Time-Lapse-Inkubator
Bereits vor zwei Jahren wurde anhand
einer groß angelegten, retrospektiven
Untersuchung gezeigt, dass die ungestörte Kultur im EmbryoScope™ TimeLapse-System, kombiniert mit einem
morphokinetischen Auswerteverfahren,
eine relative Erhöhung der klinischen
Schwangerschaftsrate um 20 % gegenüber der Kultur im Standardinkubator
bewirkt [1].
Diese Ergebnisse wurden nun im Rahmen einer prospektiven Nachfolgestudie
auf den Prüfstand gestellt. In der aktuellen Untersuchung [2] wurden Embryonen von 843 Patientinnen randomisiert
und teilweise im EmbryoScope™, teilweise im Standardinkubator kultiviert.
Zur Beurteilung der Embryonen mit dem
EmbryoScope™
Time-Lapse-System
wurde eine speziell adaptierte, morphokinetische Methode verwendet. Beim
herkömmlichen Inkubationsverfahren
wurde die etablierte, morphologische
Beurteilung eingesetzt. Die vorliegende
Studie kommt zum Ergebnis, dass unter
298
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
a
b
c
Abbildung 2: (a): Implantationsrate in % aller transferierten Embryonen; (b): Klinische Schwangerschaftsrate in % aller Behandlungen; (c): Frühabortrate. Erstellt
nach Daten aus [2].
den gewählten Bedingungen im Vergleich zu Standardverfahren Kultur und
Evaluierung der Embryonen im EmbryoScope™ eine relative Zunahme der Implantationsrate um 21 % (Abb. 2a) bewirken und zu einer relativen Erhöhung
der klinischen Schwangerschaftsrate um
23,2 % (Abb. 2b) führen. Gleichzeitig
wurde nach EmbryoScope™-Behandlung eine im Verhältnis um 35,7 % verminderte Wahrscheinlichkeit eines Frühaborts festgestellt (Abb. 2c).
Die vorliegende Studie stellt unter Beweis, dass der technologische und wissenschaftliche Vorsprung das EmbryoScope™ zu dem gemacht hat, was es
heute ist: Die Nummer 1 der Time-LapseSysteme mit unbestreitbarem Nutzen für
Kliniken und ihre Patientinnen.
Als Erfolgsgaranten beim Einsatz des
EmbryoScope™ Time-Lapse-Systems
wurden auch in der aktuellen Untersuchung eine Kombination aus stabilen Inkubationsbedingungen und der Möglichkeit zur benutzerdefinierten, morphokinetischen Embryobeurteilung identifiziert. Als Vorreiter der Time-LapseSysteme und im Unterschied zu einigen
Marktneulingen ist das EmbryoScope™
beides zugleich: Inkubator und kamerabasiertes Auswertesystem. Hohe Temperaturkonstanz und stabile Zufuhr von gereinigtem, sterilem Gas gewährleisten
die Embryokultur unter optimierten
Bedingungen ohne Temperatur- oder
pH-Schwankungen. Speziell entwickelte
Auswertealgorithmen, basierend auf einer weltweit einzigartigen Sammlung
von Implantationsdaten mit bekanntem
Ergebnis, verfeinern kontinuierlich die
morphokinetische Beurteilungsmethodik und ermöglichen gleichzeitig die ungestörte Kultur des Embryos bis zum
Zeitpunkt des Transfers.
Literatur:
Haben Sie Fragen, oder wünschen Sie
ein Angebot? Bitte kontaktieren Sie uns!
1. Meseguer M, Rubio I, Cruz M, Basile N, Marcos J,
Requena A. Embryo incubation and selection in a
time-lapse monitoring system improves pregnancy
outcome in comparison with a standard incubator; a
retrospective cohort study. Fertil Steril 2012; 98:
1481–9.
2. Rubio I, Galan A, Larreategui Z, Ayerdi F, Bellver J,
et al. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertil Steril 2014
[Epub ahead of print].
Weitere Informationen und verantwortlich für den Inhalt:
MTG Medical Technology Vertriebs-GmbH
Dr. Gerhard Weidner
D-84079 Bruckberg
Dr. Pauling-Straße 9
E-Mail: [email protected]
www.mtg-de.com
Medizintechnik
Erfolgsquote mit IVF vergleichbar
Die intrauterine Insemination (IUI) ist
die am längsten und häufigsten praktizierte Behandlung der assistierten Reproduktion. Die Erfolgsrate der IUI
liegt jedoch nur in seltenen Fällen über
10 % pro Zyklus. Umso erstaunlicher ist
es, dass sich in all den Jahren niemand
ernsthaft mit einer Verbesserung der
Technik dieser weitverbreiteten Methode
beschäftigt hat.
Mit EVIE-Slow Release Insemination
System steht nun ein neues Verfahren
zur Verfügung, das eine Verdopplung
der Schwangerschaften bei Frauen unter
35 Jahren im Vergleich zur herkömmlichen IUI verspricht.
EVIE – Pumpt Schwangerschaftsraten
in neue Höhen
EVIE ist eine kleine, mechanische Pumpe zur Einmalverwendung.
EVIE gibt Sperma über einen Zeitraum
von 4 Stunden langsam in die Gebärmutter ab, wodurch die Zeitspanne verlängert wird, in der Eizelle und Spermi-
„Aufgrund vielversprechender Zwischenergebnisse kann die EVIEMethode in Zentren, die
nicht an der Studie teilnehmen, bereits jetzt
nach ausführlicher Aufklärung angeboten werden.“
Dr. Maximilian Franz
Gynäkologe und Reproduktionsmediziner
München, Investigator Universitätsfrauenklinik Wien, Abt. f. Gyn. Endokrinlogie und
Reproduktionsmedizin
en zusammentreffen können. Dadurch
steigt die Befruchtungswahrscheinlichkeit signifikant.
Die Endergebnisse einer großen internationalen, multizentrischen Studie werden
im Herbst 2014 erwartet. Bisherige
Zwischenergebnisse von 154 Zyklen
sind vielversprechend und wurden im
März beim FertiForum in Mainz präsentiert: Die Schwangerschaftsrate verbesserte sich um das 2,2-Fache bei Frauen unter 35 Jahren. Das beste Zentrum
steigerte die Schwangerschaftsrate von
13 % auf 26,3 % über alle Altersgruppen. Diese Ergebnisse haben noch keine
statistische Signifikanz erreicht, bestätigen jedoch Erfolgsraten aus zwei früheren Studien.
Alle Informationen über EVIE inklusive
Einführungsvideos finden Sie auf
www.kairos-life.com
Welchen therapeutischen Nutzen
bietet EVIE?
– Verdoppelung der Schwangerschaftsrate pro Zyklus gegenüber
IUI bei Frauen unter 35 Jahren
– Schwangerschaftsrate vergleichbar
mit IVF/ICSI
– Weniger invasive First-line-Therapie
– Hohe Akzeptanz bei Frauen
– Leichte Handhabung, keine Änderung der klinischen Routine notwendig
Welche Kinderwunschpaare profitieren von EVIE?
–
–
–
–
Jüngere Frauen unter 35 Jahren
Männer mit leichter Subfertilität
Paare mit idiopathischer Infertilität
Frauen mit Endometriose (I–II) bei
intakten Eileitern
– Paare, die eine heterologe/donogene Insemination wünschen
Weitere Informationen und verantwortlich für den Inhalt:
KAIROS Life Sciences GmbH
A-2344 Maria Enzersdorf, Hauptstraße 5
Tel.: +43/(0)2236/710 777-0
Fax: +43/(0)2236/710 777-70
E-Mail: [email protected]
Für Deutschland:
Gynemed GmbH & Co KG
D-23738 Lensahn, Lübecker Straße 9
Tel.: +49/(0)4363/903 29-0
E-Mail: [email protected]
J Reproduktionsmed Endokrinol 2014; 11 (5–6)
299
Entgeltliche Einschaltung
IUI war gestern – EVIE ist
heute: Slow Release Insemination (SRI)
GONAL-f:
ÜBER 1 MIO. BABYS
WELTWEIT
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