M.C. Allemand

Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review*

Objectives.  To assess and quantify the relationship between polycystic ovaries (PCOs) and ovarian hyperstimulation syndrome (OHSS).

Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary rat myotubes--a potential model for PCOS-related insulin resistance.

Background Polycystic ovary syndrome (PCOS) is characterized by a hyperandrogenic state and frequently develops skeletal muscle insulin resistance. We determined whether testosterone adversely affects insulin action by increasing serine phosphorylation of IRS-1636/639 in differentiated rat skeletal muscle myotubes. The phosphorylation of Akt, mTOR, and S6K, downstream targets of the PI3-kinase-IRS-1 complex were also studied. Methods Primary differentiated rat skeletal muscle myotubes were subjected to insulin for 30 min after 16-hour pre-exposure to either low (20 ng/ml) or high (200 ng/ml) doses of testosterone. Protein phosphorylation of IRS-1 Ser636/639, Akt Ser473, mTOR-Ser2448, and S6K-Thr389 were measured by Western blot with signal intensity measured by immunofluorescence. Results Cells exposed to 100 nM of insulin had increased IRS-1 Ser636/639 and Akt Ser473 phosphorylation. Cells pre-exposed to low-dose testosterone had significantly increased insulin-induced mTOR-Ser2448 and S6K-Thr389 phosphorylation (p<0.05), and further increased insulin-induced IRS-1 Ser636/639 phosphorylation (p = 0.042) compared to control cells. High-dose testosterone pre-exposure attenuated the insulin-induced mTOR-Ser2448 and S6K-Thr389 phosphorylation. Conclusions The data demonstrated an interaction between testosterone and insulin on phosphorylation of intracellular signaling proteins, and suggests a link between a hyperandrogenic, hyperinsulinemic environment and the development of insulin resistance involving serine phosphorylation of IRS-1 Ser636/639. These results may guide further investigations of potential mechanisms of PCOS-related insulin resistance.

Ovarian hyperstimulation syndrome: steps to maximize success and minimize effect for assisted reproductive outcome

OBJECTIVE To investigate the strategies used to decrease the risk of ovarian hyperstimulation syndrome (OHSS) and their impact on pregnancy and live birth rates. DESIGN Retrospective cohort analysis. SETTING University hospital. PATIENT(S) One hundred eighty-eight patients undergoing fresh in vitro fertilization (IVF) cycles between 2000 and 2004, with peak serum estradiol levels >2500 pg/mL and presumed to be at risk for OHSS. INTERVENTION(S) Coasting and elective embryo cryopreservation were evaluated for their effect on OHSS and live birth rates. MAIN OUTCOME MEASURE(S) Pregnancy, live birth rates, and OHSS incidence. RESULT(S) Out of 188 patients at risk for OHSS, 21 patients had their cycles coasted (group 1), and elective embryo cryopreservation was performed in 32 patients (group 2). In 135 patients with no other risk factors, ovulation was triggered with human chorionic gonadotropin and embryo transfer was performed (group 3). The incidence in our IVF population was 38 out of 1002 (3.8%). The overall incidence of OHSS for those who had an estradiol level >2500 pg/mL was 20.2% (38 out of 188), and none of the patients in group 1 developed OHSS; 13 out of 32 patients in group 2 (40.6%) and 25 out of 135 (18.5%) patients in group 3 developed OHSS. The live birth rate was 38%, 40%, and 45% in groups 1, 2, and 3, respectively, and the cumulative live birth rate was 52%, 75%, and 59%, respectively. CONCLUSION(S) Elective cryopreservation of embryos with subsequent frozen embryo transfer and coasting are effective ways of maximizing pregnancy and limiting severe OHSS.

High Cumulative Live Births in Oocyte Donation Cycles with Cryopreservation of All Embryos

Background: Cryopreservation of all embryos in stimulated IVF cycles is occasionally necessary. Although it is known that frozen embryo transfer results in lower live birth rates per transfer, there is limited information regarding expected cumulative live birth rates for patients who are in this particular scenario. Methods: The objective was to evaluate long-term outcomes in cycles undergoing pronuclear cryopreservation of all embryos utilizing a retrospective analysis of 154 consecutive recipients from 1995 to 2006. Results: The cumulative rate of first live birth per retrieval was 66.2%, with a 36.4% live birth rate per frozen embryo transfer. Following an average 2.2 ± 0.98 transfers, 32.6% (17/52) of patients who never delivered had remaining embryos making the cumulative first live birth rate previously stated a conservative estimate. 11.7% of recipients had sibling deliveries from a single retrieval. Over 1/3 of the delivered recipients have remaining cryopreserved embryos and could pursue an additional pregnancy. Conclusion: These results suggest that pronuclear cryopreservation of all embryos in an oocyte donation cycle maintains good cumulative live birth rates, as well as chances for a sibling from a single retrieval. Recipients who must delay transfer can be reassured a high potential for live birth from their first donor retrieval.