OHSS FREE CLINIC
description
Transcript of OHSS FREE CLINIC
![Page 1: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/1.jpg)
OHSS FREE CLINIC
Prof Dr P Devroey
![Page 2: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/2.jpg)
The Era of a OHSS Free Clinic
By understanding biology
By using drugs differently
By innovative strategic thinking
Definition
![Page 3: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/3.jpg)
Definition of OHSS
Iatrogenic complication (!) of
“controlled” (?) ovarian stimulation
Potentially fatal (!)
Risk factor (PCOS)
Triggering mechanism of hCG ( ! )
Intriguing
![Page 4: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/4.jpg)
Intriguing
Iatrogenic Who is responsible?
Ovarian stimulation How to stimulate?
HCG is the trigger HCG to be replaced?
OHSS
![Page 5: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/5.jpg)
Ovarian hyperstimulation syndrome
01 09 2011
PubMed n : 2 275 citations
Severe OHSS
![Page 6: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/6.jpg)
Severe OHSS
IV fluid Respiratory distress (intensive care
admission) Electrolyte imbalance Dopamine to improve diuresis Heparin to prevent thrombosis Vaginal aspiration of ascitis fluid
Aboulghar SRM 2010
Form
![Page 7: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/7.jpg)
Form of OHSS
Early onset (early OHSS) up to 9 days after oocyte retrieval related to excessive ovarian response
Late onset (late OHSS) 10 days after oocyte retrieval induced by endogenously produced hCG after implantation
Papanikolaou HR 2005
Incidence
![Page 8: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/8.jpg)
Incidence of OHSS (hospitalized)
2 524 IVF/ICSI cycles
53 patients 2.1 % (95 % CI : 1.6 -
2.8)
Early OHSS (n : 31) 1.2 % (95 % CI : 0.9 - 1.8)
Late OHSS (n : 22) 0.0 % (95 % CI : 0.5 - 1.31)
Papanikolaou FS 2006
Fatal
![Page 9: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/9.jpg)
Fatal OHSS
25 years old Japanese lady
Bilateral chest pain - dyspnoea
Pleural effusion
Fatal after respiratory insufficiency
Autopsy massive pulmonary edema
Semba Patol Int 2000
Fatal
![Page 10: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/10.jpg)
Fatality due to OHSS
31 years old woman
Ovarian stimulation (Gonal F)
Fatal adult respiratory distress
syndrome
Fineschi Int J Legal Med 2006
Maternal death
![Page 11: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/11.jpg)
Maternal deathIn IVF in the Netherlands (1984 – 2008)
Death to OHSS : 3 / 100 000 IVF cycles
Respiratory distress (n : 2)
Cerebrovascular thrombosis (n : 1)
Braat HR 2010
Does it mean 30 / 1 000 000 ?
![Page 12: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/12.jpg)
At random citations
OHSS is difficult to predict, but multiple preventive strategies and protocols are being developed that may limit it
Patchava Minerva Ginecol 2009
Ovarian stimulation carries a marked risk for … ovarian hyperstimulation syndrome
Kallen Best Pract Res Clin Obstet Gynaecol 2008
![Page 13: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/13.jpg)
At random citations (continued)
Low dose hCG at the end of the
follicular phase Nargund RBO 2007
Preventive administration of IV fluid Youssef Cochrane Database Syst Rev 2011
Continuous vaginal and thoracic fluid
drainage for management of severe
ovarian hyperstimulation syndrome Ceyhan Gynecol Endocrinol 2008
![Page 14: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/14.jpg)
At random citations (continued)
Severe ovarian hyperstimulation
syndrome : an intensive care disease Humeeus Rev Med Chil 1998
Coasting no benefit D’Angelo Cochrane Database Syst Rev 2011
Dopamine antagonist significant
reduction Sherwal J Human Reprod Sci 2010
Obstetrical outcome
![Page 15: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/15.jpg)
Obstetrical outcome of IVF pregnancies in OHSS syndrome
Occurrence 40/3 504 cycles (1.4 %)
Control (80)
P
Duration of hospitalization 10 Days 0
Early OHSS 22.5 % 0
Late OHSS 75.5 % 0
Thrombo-embolic complications
10.0 % 0
Pregnancy induced hypertension
21.0 % 9 % S
Preterm labor 36.0 % 11 % S
Courbiere FS 2011
Iatrogenic ?
![Page 16: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/16.jpg)
The question : Is iatrogenic OHSS avoidable and erasable ?
Understanding different biological
mechanisms
using different drugs
using different treatment strategies
Devroey et al HR 2011
![Page 17: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/17.jpg)
Is GnRH agonist triggering an option ?
PubMed 01.03.2011 n : 83 publications
Gonadotrophin-releasing hormone agonist
triggering : the way to eliminate ovarian
hyperstimulation syndrome - a 20 years
experience
Kol Sem Reprod Med 2010
![Page 18: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/18.jpg)
GnRH agonist triggering
GnRH-a hCG
n : 84 n : 95
Age (years) 33 34
Eggs (mean) 5.9 5.2
Embryos transferred 2.5 2.3
Pregnancy rates 20 % 19 %
Segal FS 1992
Reflexion
![Page 19: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/19.jpg)
Reflexion
It is possible that down regulation
of pituitary receptors and reduced
LH support for the corpus luteum
may occur even after a single
administration of GnRH agonist
Segal FS 1992
![Page 20: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/20.jpg)
Cycle outcome
Brussels
Agonist hCG
Stimulation (in patients)
18 24
OPU (n) 18 24
ET (n) 15 20
Ongoing pregnancy rate / started cycle
1/18 (5.6 %) 10/24 (41.7 %)
Odds ratio (95 % CI) 0.11 (0.02 – 0.52)
P level = 0.005
Kolibianakis HR 2005
![Page 21: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/21.jpg)
Triggering GnRH agonist 0.2 mg Triptorelin
hCG 10 000
Vaginal progesterone
+ +
Estradiol valerate + +
Discontinuation - -
Pregnancy rate 5.6 % 41.7 %
Kolibianakis HR 2005
GnRH agonist triggering in a GnRH antagonist cycle
![Page 22: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/22.jpg)
GnRH agonist triggering in GnRH antagonist cycles in OHSS risk AIM : avoiding OHSS Patients (n : 12) > 25 follicles GnRH agonist triggering and 1 500 hCG
35 hours later COC (n : 20) Ongoing pregnancies 50 % (6/12) No OHSS
Humaidan RBMO 2009
![Page 23: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/23.jpg)
GnRH agonist triggering in GnRH antagonist cycles (RCT)
GnRH agonist + 1 500 hCG
hCG 10 000
Patients (n) 152 150
Transfer rate (%) 86 92
Delivery rate / patient 36 / 152 (24 %) 47 / 150 (31 %)
Humaidan FS 2010
![Page 24: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/24.jpg)
Oocyte donors (GnRHa donors)
Triggering GnRHa hCG P
Subjects (n) 50 50
Age (y) 25 25
rFSH dose (U) 2 300 2 300
Eggs retrieved (mean)
17 19
OHSS rate 0 / 50 8 / 50 0.03
Melo RBMO 2009
![Page 25: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/25.jpg)
Elective vitrification of all zygotes after GnRH agonist triggering
Days of stimulation (mean) 10
FSH (U) 1 900
COC (mean) 16
Ongoing pregnancy / patient 7 / 19 (37 %)
Griesinger HR 2007
![Page 26: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/26.jpg)
Oocyte donation using egg cryobanking
153 eggs
117 fertilized
47 blastocysts transferred
2.3 per ET
26 implanted (55 %)
Nagy FS 2009
![Page 27: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/27.jpg)
Oocyte banking (vitrification)
RCT P
Frozen Fresh
Ongoing pregnancy rate / ET
43.7 % 41.7 % NS
Clinical pregnancy rate / ET
55.0 % 56.0 % NS
Implantation rate 40.0 % 41.0 % NS
Similar results95 % CI : 0.7 – 1.3
Cobo HR 2010
![Page 28: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/28.jpg)
Oocyte vitrification : closed carrier
Patients N : 20
Survival rate 111 / 123 (90 %)
Fertilization rate 86 / 111 (75.5 %)
Cleavage rate (day 3) 80 / 86 (93 %)
Clinical pregnancy rate per patient 10 / 20
Ongoing pregnancy rate 9 / 20
Frozen embryo replacement 1 / 3
Cumulative Ongoing pregnancy rate per patient Implantation per warmed oocyte
10 / 20 (50 %) 14 / 123 (11.4 %)
Personal communication
![Page 29: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/29.jpg)
Oocyte vitrification after GnRH agonist triggering versus coasting
Observational study
Oocyte vitrification after GnRH agonist
triggering (n : 152)
Classical coasting (n : 96)
Egg vitrification (pregnancy rate 50 %)
Clinical coasting (pregnancy rate 30 %)
Herrero FS 2010
![Page 30: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/30.jpg)
Endometrial biopsy on the day of ovulation, natural cycle
No secretory features
![Page 31: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/31.jpg)
Endometrial biopsy on the day of oocyte retrieval, GnRH agonist and gonadotrophin stimulation cycle
Clear secretory features
![Page 32: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/32.jpg)
Endometrium histology at OPU and the probability of pregnancy
Author Stimulation Endometrial advancement
Odds ratio 95% CI P
≤ 3 days > 3 days
Clinical pregnancy rate
Ubaldi (1997) hMG/agonist 10/32 0/7
Kolibianakis (2002)
Rec-FSH/antagonist
11/49 0/6
21/81 0/13 0.22 0.06-0.89 0.03
Ongoing pregnancy rate
Ubaldi (1997) hMG/agonist 10/32 0/7
Kolibianakis (2002)
Rec-FSH/antagonist
8/49 0/6
18/81 0/13 0.23 0.05-0.98 0.05
Kolibianakis FS 2002
![Page 33: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/33.jpg)
Advanced endometrial maturation - no pregnancies
Upregulated genes
SERPINB6
FOXO3A
SOX17
CDC42
Van Vaerenbergh I HR 2009
![Page 34: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/34.jpg)
CONCLUSION
Past
Down regulation with GnRH agonist
HCG for final egg maturation
OHSS ≈ 2 %
Today
For first cycle always GnRH antagonist
GnRH agonist triggering if at risk for OHSS Freeze all
ET of fresh embryo
adding low dose hCG in
luteal phase
OHSS 0 %
![Page 35: OHSS FREE CLINIC](https://reader031.fdocuments.us/reader031/viewer/2022020920/56815854550346895dc5aeb2/html5/thumbnails/35.jpg)
CODA
(A) Optimization of
stimulation
(B) Optimization of
embryology
(C) Optimization of
endometrial
implantation potential
(A) GnRH antagonist and
GnRH agonist to trigger
(F) Freeze all
oocytes/embryos
(R) Replacement in receptive
endometrium
(spontaneous or artificial)
OHSS FREE CLINICAFR segmentation strategy