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.

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.

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-1(636/639) 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 Ser(636/639), Akt Ser(473), mTOR-Ser(2448), and S6K-Thr(389) were measured by Western blot with signal intensity measured by immunofluorescence. RESULTS: Cells exposed to 100 nM of insulin had increased IRS-1 Ser(636/639) and Akt Ser(473) phosphorylation. Cells pre-exposed to low-dose testosterone had significantly increased insulin-induced mTOR-Ser(2448) and S6K-Thr(389) phosphorylation (p<0.05), and further increased insulin-induced IRS-1 Ser(636/639) phosphorylation (p = 0.042) compared to control cells. High-dose testosterone pre-exposure attenuated the insulin-induced mTOR-Ser(2448) and S6K-Thr(389) 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 Ser(636/639). These results may guide further investigations of potential mechanisms of PCOS-related insulin resistance.

Role of saline infusion sonography in uterine evaluation before frozen embryo transfer cycle.

OBJECTIVE: To determine the role of saline infusion sonography (SIS) in uterine evaluation before a frozen embryo transfer (FET) cycle. DESIGN: Retrospective cohort analysis. SETTING: University hospital. PATIENT(S): Thirty-six patients who had uterine evaluation by SIS before FET cycle. INTERVENTION(S): The SIS was performed in the follicular phase of the menstrual cycle before the actual FET cycle. MAIN OUTCOME MEASURE(S): The SIS findings, clinical pregnancy rate (PR), ongoing PR, and correlation between positive SIS findings with and without subsequent treatment and pregnancy outcome. RESULT(S): Positive SIS findings were found in 11/36 patients (30.5%), which included uterine septum (9.0%), endometrial polyp (45.4%), intramural fibroid with normal cavity (9.0%), cystic endometrial changes (9.0%), cervical stenosis (18.1%), and calcification with normal cavity (9.0%). The overall clinical PR in all groups was 51.4%, with an ongoing PR of 45.7%. Patients with positive SIS finding who underwent subsequent hysteroscopic correction (7/11) had a clinical PR of 85.7% as compared to 54.1% in patients with normal uterine cavity (24/35). Patients with positive SIS findings and no operative hysteroscopy (4/11) had a clinical PR of 50% and pregnancy loss rate of 100%. CONCLUSION(S): Obtaining an SIS before the FET cycle can be helpful in the detection of uterine abnormalities. If time since uterine evaluation has been more than 1-2 years, performing an SIS is recommended as subsequent correction of the anomalies may improve FET outcome.

Diagnosis of polycystic ovaries by three-dimensional transvaginal ultrasound.

OBJECTIVE: To study diagnostic thresholds for polycystic ovary (PCO). DESIGN: Retrospective cohort study. SETTING: Academic hospital. PATIENT(S): Normoandrogenic ovulatory women and patients with polycystic ovary syndrome (PCOS). INTERVENTION(S): Two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound. MAIN OUTCOME MEASURE(S): The mean follicle number per ovary (FNPO) of both ovaries and the maximum number follicles in a single sonographic plane (FSSP) of either ovary were determined using 3D transvaginal ultrasound. Ovarian volume was determined using 2D transvaginal ultrasound. RESULT(S): Twenty-nine normoandrogenic ovulatory women were compared with 10 patients with PCOS. Diagnostic thresholds for PCO with 100% specificity as determined by receiver operator characteristic (ROC) curves were > or =20 for mean FNPO, > or =10 for maximum FSSP, and > or =13 cm3 for ovarian volume. Both 2D and 3D transvaginal ultrasound were highly accurate in the diagnosis of PCO as determined by areas under the curve (AUC) that were >90% for all three measures. CONCLUSION(S): Mean FNPO and maximum FSSP by 3D transvaginal ultrasound have comparable high accuracy for diagnosis of PCO. The diagnostic threshold with 100% specificity for mean FNPO is > or =20, which is greater than suggested by the Rotterdam Consensus Workshop in 2003. Use of the consensus standard, consequently, may result in overdiagnosis of PCO. A threshold of > or =20 mean FNPO using 3D transvaginal ultrasound may be appropriate to minimize false-positive diagnoses of PCO.

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). DATA SOURCES: Published studies, any language, identified through MEDLINE, EMBASE, BIOSIS, Web of Science, and bibliographies. Studies were selected if exposure (ultrasound findings of PCO before treatment) and outcome (OHSS) could be abstracted to two-by-two tables. RESULTS: Ten studies, meeting inclusion and exclusion criteria, were analyzed. When PCO were present, the combined odds ratio for OHSS was 6.8 (95% confidence interval 4.9-9.6). CONCLUSION: There is a significant and consistent relationship between PCO and OHSS. When PCO are present before treatment with assisted reproduction, deliberate policies to moderate treatment appear justified.