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OHSS FREE CLINIC. Prof Dr P Devroey. The Era of a OHSS Free Clinic. By understanding biology By using drugs differently By innovative strategic thinking. Definition. Definition of OHSS. Iatrogenic complication (!) of “controlled” (?) ovarian stimulation

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Ohss free clinic

OHSS FREE CLINIC

Prof Dr P Devroey


The era of a ohss free clinic

The Era of a OHSS Free Clinic

  • By understanding biology

  • By using drugs differently

  • By innovative strategic thinking

Definition


Definition of ohss

Definition of OHSS

  • Iatrogenic complication (!) of “controlled” (?) ovarian stimulation

  • Potentially fatal (!)

  • Risk factor (PCOS)

  • Triggering mechanism of hCG ( ! )

Intriguing


Intriguing

Intriguing

  • IatrogenicWho is responsible?

  • Ovarian stimulationHow to stimulate?

  • HCG is the triggerHCG to be replaced?

OHSS


Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome

  • 01 09 2011

  • PubMed n : 2 275 citations

Severe OHSS


Severe ohss

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


Form of ohss

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


Incidence of ohss hospitalized

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


Fatal ohss

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


Fatality due to ohss

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


Maternal death in ivf in the netherlands 1984 2008

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 ?


At random citations

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


At random citations continued

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


At random citations continued1

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


Obstetrical outcome of ivf pregnancies in ohss syndrome

Obstetrical outcome of IVF pregnancies in OHSS syndrome

Courbiere FS 2011

Iatrogenic ?


The question is iatrogenic ohss avoidable and erasable

The question : Is iatrogenic OHSS avoidable and erasable ?

Understanding different biological mechanisms

using different drugs

using different treatment strategies

Devroey et al HR 2011


Is gnrh agonist triggering an option

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


Gnrh agonist triggering

GnRH agonist triggering

Segal FS 1992

Reflexion


Reflexion

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


Cycle outcome

Cycle outcome

Kolibianakis HR 2005

Odds ratio (95 % CI) 0.11 (0.02 – 0.52)

P level = 0.005


Gnrh agonist triggering in a gnrh antagonist cycle

GnRH agonist triggering in a GnRH antagonist cycle

Kolibianakis HR 2005


Gnrh agonist triggering in gnrh antagonist cycles in ohss risk

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


Gnrh agonist triggering in gnrh antagonist cycles rct

GnRH agonist triggering in GnRH antagonist cycles (RCT)

Humaidan FS 2010


Oocyte donors gnrha donors

Oocyte donors (GnRHa donors)

Melo RBMO 2009


Elective vitrification of all zygotes after gnrh agonist triggering

Elective vitrification of all zygotes after GnRH agonist triggering

Griesinger HR 2007


Oocyte donation using egg cryobanking

Oocyte donation using egg cryobanking

  • 153 eggs

  • 117 fertilized

  • 47 blastocysts transferred

  • 2.3 per ET

  • 26 implanted (55 %)

    Nagy FS 2009


Oocyte banking vitrification

Oocyte banking (vitrification)

Cobo HR 2010


Oocyte vitrification closed carrier

Oocyte vitrification : closed carrier

Personal communication


Oocyte vitrification after gnrh agonist triggering versus coasting

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


Endometrial biopsy on the day of ovulation natural cycle

Endometrial biopsy on the day of ovulation, natural cycle

No secretory features


Endometrial biopsy on the day of oocyte retrieval gnrh agonist and gonadotrophin stimulation cycle

Endometrial biopsy on the day of oocyte retrieval, GnRH agonist and gonadotrophin stimulation cycle

Clear secretory features


Endometrium histology at opu and the probability of pregnancy

Endometrium histology at OPU and the probability of pregnancy

Kolibianakis FS 2002


Advanced endometrial maturation no pregnancies

Advanced endometrial maturation - no pregnancies

  • Upregulated genes

    • SERPINB6

    • FOXO3A

    • SOX17

    • CDC42

      Van Vaerenbergh I HR 2009


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 %

CONCLUSION


Ohss free clinic

Optimization of stimulation

Optimization of embryology

Optimization of endometrial implantation potential

GnRH antagonist and GnRH agonist to trigger

Freeze all oocytes/embryos

Replacement in receptive endometrium (spontaneous or artificial)

CODA

OHSS FREE CLINIC

AFR segmentation strategy


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