Outcomes of Elective Cryopreservation of All Embryos in Women at High Risk of Developing Ovarian Hyperstimulation Syndr

1. Outcomes of Elective Cryopreservation of All Embryos in Women at High Risk of Developing Ovarian Hyperstimulation Syndrome Kelly S. Wiersema, MD Douglas C. Daly, MD Grand Rapids Medical Education and Research Center Michigan State University College of Human Medicine Grand Rapids, Michigan

2. Ovarian Hyperstimulation Syndrome(OHSS) Known risk of FSH treatment for infertility Ovarian enlargement, shifts in body fluids Self limited in patients who do not conceive Uncommon, but potentially fatal during early pregnancy How can we prevent or limit OHSS? Release of vasoactive substances by the ovaries under hCG stimulation is key in triggering the syndrome. Massive shifts of fluid from intravascular compartment to 3rd space causing intravascular depletion and hemoconcentration.Release of vasoactive substances by the ovaries under hCG stimulation is key in triggering the syndrome. Massive shifts of fluid from intravascular compartment to 3rd space causing intravascular depletion and hemoconcentration.

3. Who is at risk? Polyfollicular ovaries (high oocyte number) High estradiol concentration during ovarian stimulation Large number of growing follicles during ovarian stimulation Rates of severe OHSS are 0.5 to 2%.Rates of severe OHSS are 0.5 to 2%.

4. Pregnancy and OHSS Becoming pregnant during a stimulation cycle can exacerbate and prolong the syndrome Endogenous or exogenous human chorionic gonadotropin (hCG) influences the duration and severity of the syndrome Critical event in development of OHSS is administration of hCG. Moderate or severe OHSS will typically present in luteal phase secondary to ovulatory hCG or in early gestation from endogenous hCG production. If no pregnancy is established, syndrome rapidly resolves with onset of menses and rarely progresses to severe form. If pregnancy is established, exacerbation of the syndrome is seen and can persist for up to 12 weeks gestation and is more often seen with multiple gestations.Critical event in development of OHSS is administration of hCG. Moderate or severe OHSS will typically present in luteal phase secondary to ovulatory hCG or in early gestation from endogenous hCG production. If no pregnancy is established, syndrome rapidly resolves with onset of menses and rarely progresses to severe form. If pregnancy is established, exacerbation of the syndrome is seen and can persist for up to 12 weeks gestation and is more often seen with multiple gestations.

5. Cryopreservation of All Embryos Patient undergoes oocyte retrieval and fertilization All viable embryos are then cryopreserved The risk of pregnancy is eliminated in the stimulation cycle Patient undergoes transfer of embryos in future, nonstimulated cycle

6. Research Question What are the pregnancy outcomes of these patients? Hypothesis Initiation of pregnancy and pregnancy outcome will be as good for patients undergoing cryopreservation of all embryos when compared to patients at risk for OHSS who undergo fresh transfer of embryos in the stimulated cycle.

7. Methods Retrospective chart review Private IVF clinic in Grand Rapids, MI

8. Study group Charts reviewed from January 2000 to October 2007 Patients considered to be at risk for and/or exhibiting signs/symptoms of OHSS Cryopreservation of all embryos Subsequent frozen transfer in future nonstimulated cycle 33 patients with

9. Control Group Charts reviewed from January 2004 to August 2006 Patients with a peak estradiol concentration of 4000pg/ml or greater Thought NOT to be at risk and/or signs of hyperstimulation syndrome Fresh transfer of embryos in the stimulated cycle 41 patients

10. Outcomes Clinical pregnancy rate per patient and transfer Livebirth rate per patient and transfer Multiple pregnancy rate Rates of moderate or severe OHSS

11. Results

12. Results

13. Clinical Pregnancy Rate

14. Livebirth Rate

15. Multiple Pregnancy Rate Fresh transfer: 5 twins, 1 triplet Cryopreservation: 8 twins, 3 tripletsFresh transfer: 5 twins, 1 triplet Cryopreservation: 8 twins, 3 triplets

16. Discussion Cochrane review in 2002 showed insufficient evidence to support cryopreservation Some studies have shown inferior pregnancy rates when all embyros were cryopreserved and patients underwent frozen embryo transfer Other strategies have been used to try and prevent OHSS Cycle cancellation, IV albumin, withholding gonadotropin administration (coasting)Cycle cancellation, IV albumin, withholding gonadotropin administration (coasting)

17. Discussion This study shows excellent pregnancy and livebirth rates Rates of moderate and severe OHSS in the study group were high Duration of OHSS was short (resolved by LPD #12) and all patients treated as outpatients

18. Conclusion Potentially higher, though not statistically significant, increase in pregnancy and livebirth rates Given the excellent pregnancy rates, this is a viable option to manage patients at high risk of OHSS Need further studies with larger number of patients, and prospective trials