Annual Report 2014 URG

Annual Report 2014 URG
Unit of Reproductive Medicine
Regional hospital ‘Heilig Hart’ in Leuven, Belgium
Results of the first year in the new IVF lab of LIFE,
the Leuven Institute for Fertility and Embryology.
TABLE OF CONTENTS
PREFACE
1. THE PATIENT
Age distribution of the fresh IVF cycles.
2. RESULTS OF THE IVF AND ICSI CYCLES
A.
B.
C.
D.
E.
F.
Fertilization rates at IVF and ICSI
Implantation rates
Pregnancy rates
Influence of the moment of embryo transfer
Cumulative pregnancy rates
Results of the cryo cycles
3. RESULTS OF THE INSEMINATION CYCLES
4. AREAS OF EXPERTISE
5. WHO IS WHO?
6. PUBLICATIONS OF THE TEAM MEMBERS OF LIFE IN 2014 AND
THE ORGANISATION OF THE 23rd ANNUAL ESGE CONGRESS IN BRUSSELS, 24-27/09/2014
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 2
PREFACE
"When performance is measured, performance improves.
When performance is measured and reported, the rate of improvement accelerates"
LIFE, the Leuven Institute for Fertility and Embryology, has been devoted with heart and soul to the
exploration and treatment of infertility since 1984, i.e. more than 30 years. Besides these clinical
activities, LIFE always had a strong interest in clinical and scientific research. This not only resulted in
numerous publications in peer reviewed scientific journals and an active participation in many
international congresses, but also in the development of a minimally invasive endoscopic exploration
technique for female infertility, i.e. the transvaginal hydrolaparoscopy, and in the realization of
international partnerships to promote multicentric scientific research.
In 2013 the “Unit voor Reproductieve Geneeskunde (URG)” (i.e. the Reproductive Medicine Unit) at
the ‘Heilig Hart’ (i.e. Dutch for Holy Heart) hospital in the city centre of Leuven, was completely
renovated, the icing of the cake being the realization of a state of the art high-tech IVF lab.
These efforts now start to bear fruit with implantation and cumulative pregnancy rates we, together
with the whole team, are really proud of.
Many companies publish annual reports to distribute spreadsheets among share- and stakeholders,
competitors and other interested parties. This is of course more than just looking back. It also reflects
a vision towards the future, to distinguish between the good things and the things that need to be,
can be and will be improved. Our shareholders are the colleagues who refer patients to us: the
patient’s GP’s and their specialists. Besides our daily contacts with our patients these figures and
statistics give you a clear feedback on the care we provide. Our patients are our stakeholders. Their
problem of infertility is our challenge, our motivation and incentive. These figures concern them in
the first place. More transparency in health care is becoming unavoidable. And that is exactly what
we want to offer you with this report.
The LIFE team
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 3
1. THE PATIENT
Age distribution in the IVF cycles.
In 47% of our cycles the patients are younger than 36 years of age.
In 53% of the cycles patients are older than 35.
Distribution of patient age
groups in IVF cycles (%)
50
47,2
40
31,7
30
21,1
20
10
0
-35]
[36-39]
[40-
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 4
2. IVF AND ICSI RESULTS
A. Fertilisation rates at IVF and ICSI
In patients younger than 36 the chance of an oocyte getting fertilized in our lab is 67,5 % with
ICSI and 56,3 % with IVF.
Fertilisation rates following IVF and ICSI
75,6
80
67,5
60
69,5
66,2
56,2
52,9
42,6
39,4
Fert% ICSI
40
Fert% IVF
20
0
-35]
[36-39]
[40-
ALLE
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 5
B. Implantation rates
Here we look at the chance of an embryo implanting in the uterine cavity following the
embryo transfer, i.e. the percentage of embryos which successfully undergo implantation
compared to the number of embryos transferred in a given period. In practice, it is
calculated as the number of intrauterine gestational sacs observed by transvaginal
ultrasonography divided by the number of transferred embryos.
Implantation rates
per attempt and per age group
36,5
35,8
40,0
35,0
30,9
28,5
30,0
25,0
21,2
20,0
15,1
15,0
16,1
later attempts
8,6
10,0
1st attempt
5,0
0,0
%
<36
40,0
35,0
36-39
>39
Totaal
Implantation rates
per age group
36,0
30,0
25,0
20,0
15,0
10,0
23,8
<36
36-39
20,6
>39
11,4
Total
5,0
0,0
In Belgium the law regarding medically assisted reproduction requires that patients
younger than 36 can only have SET (i.e. a single embryo transfer) at their first IVF attempt
and also at their second attempt whenever a top embryo is recognized. In all other cases
patients of that age group can have DET (i.e. a double embryo transfer). In the age group
above 39 (i.e. 40 and older) there is no limitation with regard to the number of embryos
that can be transferred. In the age group between 36 and 39 maximum 2 fresh embryos can
be replaced at the 1st and 2nd attempt and maximum 3 embryos at all subsequent attempts.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 6
C. Pregnancy rates per embryo transfer (ET)
Here we look at the chance of a pregnancy per embryo transfer, regardless of the number of
embryos that were transferred: 47% of all fresh embryo transfers in patients younger than 36
result in a pregnancy; 36% was ongoing.
Pregnancy rates per embryo transfer
50
40
47,2
35,8
37,1
29,1
30
24,6
ZW %
20
ONG ZW %
10,9
10
0
<36 jaar
[36-39]
[40
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 7
D. Influence of the moment of embryo transfer
47% of all fresh embryo transfers was performed at the first cellular division, i.e. day 2
38% of all fresh embryo transfers was performed at the second cellular division, i.e. day 3
10% of all fresh embryo transfers was performed at the fourth cellular division, i.e. day 5
Pregnancy rates per embryo transfer
58,9
60%
45%
44,6
41,5
37,6
27,0
30%
24,8
15%
0%
DAG2
DAG3
zw%/ET
DAG5
ZW ONG%
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 8
E. Cumulative pregnancy rates
Cumulative pregnancy rates, which is the overall chance of a birth, e.g. from the use of all the
fresh and frozen embryos from a given IVF cycle, or from the use of all the fresh and frozen
embryos of several IVF cycles. We calculated the cumulative pregnancy rate of all embryos, fresh
and frozen, of all patients starting IVF in our new setting until one year later.
More than 75% of all the young patients is pregnant within the frame of 2 IVF attempts and in
68,8% of these young patients the pregnancy is ongoing!
And these results are not complete yet!
35,5% of the patients that were not pregnant following their 1st attempt did not start their 2nd IVF
attempt as of yet; 36,2% of the patients that were not pregnant following their 2nd attempt did
not start their 3rd IVF attempt as of yet; 44,8% of the patients that did not conceive following
their 3rd IVF attempt did not start their 4th attempt as of yet.
So these cumulative pregnancy rates will continue to increase!
CUM ZW% / ET
[36-39j]
≤35j
≥40j
90,00
81,3
82,1
76,8
80,00
74,2
77,3
68,2
70,00
60,7
60,00
56,1
58,5
50,0
50,00
43,9
36,6
40,00
30,00
20,00
10,00
,00
P1
P2
P3
P4
P1
P2
P3
P4
P1
P2
P3
P4
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 9
F. CRYO RESULTS 2014
The pregnancy rate following an own embryo cryo cycle is 32,2% and the ongoing pregnancy rate in
that case is 20,5%. This is the global result of all age groups combined. The following graph also
shows you the results per age group.
Pregnancy rate following the transfer of
thawed own embryos
40
36,9
32,2
30
23,5
20
24,7
22,7
15,7
20,5
14,7
10
0
36 min
36-38
39 -plus
ZW%
Eindtotaal
ONG
Day 5 embryos give a higher pregnancy rate, fresh or frozen/thawed.
Unlike the situation in fresh cycles, the pregnancy rate of Day 3 frozen/thawed embryos is clearly
higher than of Day 2 embryos.
In view of these good results with Day 5 cryotransfers, a randomized prospective trial is currently
ongoing in our department to determine the optimal moment to freeze the embryos, either on Day 2
or 3 on the one hand, or on Day 5 on the other. We particularly await the results of the cumulative
pregnancy rates of the Day 5 cryo program before deciding to allow all embryos, including the fresh
ones, to grow till Day 5, i.e. the blastocyst stage.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 10
3. RESULTS OF THE INSEMINATIONS
Pregnancy rate per cycle.
In 2014 12,2% of the IUI (‘intra-uterine insemination’) cycles led to a pregnancy; 11% is ongoing.
For AID (artificial insemination with donor sperm) the pregnancy rate was 18,6% in 2014, with
14,5% as the ongoing pregnancy rate.
IUI & AID results 2014
20
18,6
14,5
15
12,2
11,0
PR (%)
10
ongoing PR (%)
5
0
IUI-HH
KID-HH
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 11
If we make a classification based on the 3 age groups:


23,9% of the AID cycles in patients younger than 36 led to a pregnancy
whereas only 14,4% of the IUI cycles with sperm of the partner resulted in a pregnancy in
that same age group.
Unsurprisingly donor cycles give a much higher pregnancy rate.
IUI & AID pregnancy rates / age group in 2014
23,9
25
20,9
20
18,4
16,4
15
14,4
12,6
PR (%)
10
8,6
ongoing PR (%)
8,6
6,7 6,7
5
2,3
2,3
0
-35]
[36-39]
IUI
[40-
-35]
[36-39]
[40-
AID
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 12
4. AREAS OF EXPERTISE
A. Transvaginal hydrolaparoscopy
If endoscopy is the gold standard in
the female fertility exploration, then
the in LIFE developed transvaginal
hydrolaparoscopy (THL or TVL) surely
meets all its criteria on a patientfriendly and outpatient manner.
B. Endometriosis surgery
In 3 decades we developed a
significant expertise in the
endoscopic treatment of both
minimal and severe ovarian
and/or rectovaginal
endometriosis.
C. Hysteroscopy
Despite all techniques the uterus plays
a crucial role for embryo implantation.
Therefore, the hysteroscopical
correction of any deviation has always
been a priority in our center. Recently
the LIFE team developed a new
instrument, a so called spirotome, to
take biopsies of the subendometrial
zone for the diagnosis of
abnormalities of the junctional zone
and/or adenomyosis.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 13
D. Surgical repair of the niche underneath the scar of a C-section
The formation of a niche underneath the scar in the uterus following a caesarean section
is a relatively recent and underestimated problem, which can cause infertility. Various
surgical procedures such as laparoscopic excision under hysteroscopic guidance,
hysteroscopically directed bipolar coagulation, etc. can provide a solution here.
E. Tubal surgery
Our team has built an impressive
expertise in microsurgical tubal
reanastomosis in a large series of
patients, the results and pregnancy
rates of which were published in Fertil
Steril (2009; 92 (4): 1198-1202). To
date, tubal surgery remains a valuable
option for selected patients, despite
the good results of IVF.
F. Expertise for congenital malformations
Dr. Gordts and Dr. Campo
contributed to the ESHRE/ESGE
consensus on the classification of
congenital anomalies of the female
genital tract. (Human Reproduction
2013; 28 (8): 2032-2044)
G. 3D and 4D ultrsonography
3D and 4D ultrasound is the gold standard
to identify uterine anomalies and irregularities,
in experienced hands with almost the same
efficacy as with an MRI.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 14
5. WHO IS WHO?
Dr. Stephan Gordts
(founder of LIFE, scientific director)
Dr. Patrick Puttemans
(head of URG, administrator of the bank of human
gametes & embryos and head of the 1day surgery
department at the Heilig Hart hospital)
Dr. Rudi Campo
(coordinator foreign patients within LIFE,
director of +he European Academy at ESGE,
consultant at the ZOL hospital in Genk,
former president of the ESGE)
Dr. Sylvie Gordts
(head of the URG IVF lab, PGD-PGS program
laparoscopic myomectomies, laparoscopic surgery of
ovarian and deep rectovaginal endometriosis)
Dr. Marion Valkenburg
(egg donation program, expert second opinion of patients
coming from the Netherlands)
Dr. Isabelle Segaert
(repeated implantation failure, adenomyosis
3D and 4D vaginal ultrasonography)
Emeritus Prof. Dr. Ivo Brosens
(scientific support)
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 15
6. Publications of/with team members of LIFE in 2014 &
the organization of the ESGE Congress in Brussels in 2014
1. Benagiano G, Brosens I. The multidisciplinary approach. Best. Pract. Res. Clin. Obstet.
Gynaecol. 2014:28(8):1114-22.
2. Benagiano G, Brosens I. In utero exposure and endometriosis. J. Matern. Fetal
Neonatal Med. 2014: 27(3): 303-8.
3. Benagiano G, Brosens I, Habiba M. Adenomyosis: a life-cycle approach. Reprod.
Biomed. Online. 2014.
4. Benagiano G, Brosens I, Lippi D. The history of endometriosis. Gynecol. Obstet. Invest
2014: 78: 1-9.
5. Benagiano G, Bastianelli C, Farris M, Brosens I. Selective progesterone receptor
modulators: an update. Expert. Opin. Pharmacother. 2014: 15(10): 1403-15.
6. Benagiano G, Brosens I, Habiba M. Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum. Reprod. Update. 2014: 20(3):
386-402.
7. Brosens I, Gordts S, Puttemans P (2014): Endometriose, van neonaat tot adolescent.
Gunaïkeia, 19 (8), 8-11.
8. Brosens I, Benagiano G. Pregnancy and reproductive health after solid organ
transplantation. Editorial in Best. Pract. Res. Clin. Obstet. Gynaecol. 2014: 28(8): 1113.
9. Brosens I, Gordts S, Puttemans P, Benagiano G. Pathophysiology proposed as the basis
for modern management of the ovarian endometrioma. Reprod. Biomed. Online.
2014: 28: 232-8.
10. Brosens I, Brosens JJ, Benagiano G. The risk of obstetrical syndromes after solid organ
transplantation. Best. Pract. Res. Clin. Obstet. Gynaecol. 2014: 28(8): 1211-21.
11. Brosens I, Gordts S, Puttemans P (2014): Endometriose, van neonaat tot adolescent.
Nederlands Tijdschrift voor Obstetrie en Gynaecologie, 127, 442-7.
12. Brosens I, Gordts S, Puttemans P. “La crise génitale du nouveau-né” and early onset
endometriosis: the risks of delayed diagnosis. Références en Gynécologie Obstétrique
2014: 17 (1): 1-5.
13. Campo R, Puga M, Meier FR, Wattiez A, De Wilde RL. Excellence needs training
"Certified programme in endoscopic surgery". Facts.Views.Vis.Obgyn. 2014: 6: 240-4.
14. Campo R., R. Meier, N. Dhont, G. Mestdagh, W. Ombelet. Implementation of
hysteroscopy in an infertility clinic: The one-stop uterine diagnosis and treatment. Facts
Views Vis Obgyn, 2014, 6 (4): 235-9
15. De Neubourg D, Bogaerts K, Wyns C, Camus M, Delbaere A, Delvigne A, De Sutter P,
Dubois M, Gordts S, Lejeune B, Leroy F, Vandekerckhove F, D'Hooghe T. Reply: the
danger of ignoring pregnancy and delivery rates in ART. Hum. Reprod. 2014: 29: 18301.
16. Gargett CE, Schwab KE, Brosens JJ, Puttemans P, Benagiano G, Brosens I. Potential
role of endometrial stem/progenitor cells in the pathogenesis of early-onset
endometriosis. Mol. Hum. Reprod. 2014: 20: 591-8.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 16
17. Grimbizis GF, Gordts S, Di Spiezio SA, Brucker SY, De Angelis C, Gergolet M, Li TC, Tanos
V, Brolmann HH, Gianaroli L, Campo R. Reply: are the ESHRE/ESGE criteria of female
genital anomalies for diagnosis of septate uterus appropriate? Hum. Reprod. 2014: 29:
868-9.
18. Gordts S, Campo R, Brosens I. Hysteroscopic diagnosis and excision of myometrial
cystic adenomyosis. Gynecol.Surg. 2014: 11: 273-8.
19. Gordts S, Puttemans P, Gordts S, Valkenburg M, Brosens I, Campo R. Transvaginal
endoscopy and small ovarian endometriomas: Unravelling the missing link? Gynecol.
Surg. 2014: 11 (1): 3-7.
20. Klerkx E. , M. Janssen, I. Van Der Auwera, R. Campo, J. Goossens, A. Vereecken, W.
Ombelet. A Simplified IVF Laboratory Method. Facts Views Vis. ObGyn, 2014,
Monograph: 4-5
21. Lopes AS1, Frederickx V, Van Kerkhoven G, Campo R, Puttemans P, Gordts S. Survival,
re-expansion and cell survival of human blastocysts following vitrification and warming
using two vitrification systems. J Assist Reprod Genet. 2014 Nov 9.
22. Meier R. Furst, R. Campo. Book Article "T-Shaped Uterus." In: Female Genital Tract
Congenital Malformations: Classification, Diagnosis, and Management Edited by Drs.
G.F. Grimbizis, R Campo, B.C. Tarlatzis and S. Gordts. Springer 2014.
23. Ombelet W, Van Blerkom J, Klerkx E, Janssen M, Dhont N, Mestdagh G, Nargund G,
Campo R. The (t)WE lab Simplified IVF Procedure: First Births after freezing/thawing.
Facts Views Vis. Obgyn. 2014;6(1):45-9.
24. Puttemans P, Gordts S, Valkenburg M, Campo R, Gordts Sy, Brosens I. Endometriose bij
de adolescent: proactieve diagnose en behandeling ter preventie van
onvruchtbaarheid. Tijdschrift voor Geneeskunde 2014: 70(6): 302-10.
25. Thijssen A, Klerkx E, Huyser C, Bosmans E, Campo R, Ombelet W. Influence of
temperature and sperm preparation on the quality of spermatozoa. Reprod. Biomed.
Online. 2014: 28: 436-42.
26. Van Blerkom J, Ombelet W, Klerkx E, Janssen M, Dhont N, Nargund G, Campo R. First
births with a simplified culture system for clinical IVF and embryo transfer. Reprod.
Biomed. Online. 2014: 28: 310-20.
27. Venetis CA, Papadopoulos SP, Campo R, Gordts S, Tarlatzis BC, Grimbizis GF. Clinical
implications of congenital uterine anomalies: a meta-analysis of comparative studies.
Reprod. Biomed. Online. 2014: 29(6): 665-83.
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 17
URG * Unit voor Reproductieve Geneeskunde * Regionaal ziekenhuis Heilig Hart Leuven
Naamsestraat 105, 3000 Leuven * Tel. +32 16 209030 * Fax +32 16 209040 * [email protected]
p. 18