Mira Aubuchon

Antichlamydial Antibodies, Human Fertility, and Pregnancy Wastage

Genital infections with Chlamydia trachomatis (C. trachomatis) continue to be a worldwide epidemic. Immune response to chlamydia is important to both clearance of the disease and disease pathogenesis. Interindividual responses and current chlamydial control programs will have enormous effects on this disease and its control strategies. Humoral immune response to C. trachomatis occurs in humans and persistent antibody levels appear to be most directly correlated with more severe and longstanding disease and with reinfection. There is a close correlation between the presence of antichlamydial antibodies in females and tubal factor infertility; the closest associations have been found for antibodies against chlamydial heat shock proteins. The latter antibodies have also been shown to be useful among infertile patients with prior ectopic pregnancy, and their presence has been correlated with poor IVF outcomes, including early pregnancy loss. We review the existing literature on chlamydial antibody testing in infertile patients and present an algorithm for such testing in the infertile couple.

Effects of polycystic ovarian syndrome on in vitro fertilization–embryo transfer outcomes are influenced by body mass index

OBJECTIVE To determine whether polycystic ovary syndrome (PCOS) adversely impacts IVF-embryo transfer outcomes in obese compared to lean patients. DESIGN Retrospective chart review. SETTING University-affiliated infertility program. PATIENT(S) Lean non-PCOS (n = 52), lean PCOS (n = 6), obese non-PCOS (n = 18), and obese PCOS (n = 10). INTERVENTION(S) Ninety-four fresh nondonor IVF-embryo transfer cycles analyzed. MAIN OUTCOME MEASURE(S) Cycle characteristics, clinical pregnancy (PR) and live birth rates. RESULT(S) Lean PCOS had more dominant follicles (12.2 +/- 6.0 vs. 7.7 +/- 3.6), retrieved oocytes (22.2 +/- 9.2 vs. 12.6 +/- 5.8), and frozen embryos (5 +/- 4.6 vs. 1.4 +/- 2.6) than lean non-PCOS. Lean PCOS also used fewer gonadotropin ampules (18.8 +/- 6.0 vs. 29.2 +/- 14.2), but had more retrieved oocytes (22.2 +/- 9.2 vs.14.3 +/- 4.9) than obese PCOS. Obese non-PCOS had better-grade embryos (2.1 +/- 0.8 vs. 2.7 +/- 0.8) and fewer embryos transferred (2.4 +/- 0.6 vs. 2.9 +/- 0.6) than obese PCOS, but more embryos frozen than lean non-PCOS (3.2 +/- 3.2 vs. 1.4 +/- 2.6). Implantation rates trended downward in obese patients with PCOS, but no other differences were observed. CONCLUSION(S) Patients with PCOS with a body mass index (BMI) in the lean rather than the obese range have more favorable assisted reproductive technology (ART) cycle characteristics but show no clinical outcome differences.

Case series of rosiglitazone used during the first trimester of pregnancy

Prior to 2007, use of the insulin sensitizer metformin was widely advocated in patients with polycystic ovarian syndrome (PCOS) both to promote ovulation and decrease the incidence of PCOS-associated obstetrical complications. However, the gastrointestinal disturbances associated with metformin led many to discontinue its use. Rosiglitazone is an insulin sensitizer that, because of minimal associated gastrointestinal disturbance, was used as an alternative to metformin in PCOS patients. From 2003 to 2005, 8 women with PCOS unable to tolerate metformin used rosiglitazone for ovulation induction and during their first 12 weeks of gestation. All delivered healthy babies at term, without obstetric complications or congenital anomalies. However, given recent evidence that disputes the reproductive benefits of insulin sensitization for PCOS and that raises safety concerns of rosiglitazone, we are no longer using it for PCOS treatment.

Preeclampsia: Animal models for a human cure

Preeclampsia (PE) affects ∼5% of human pregnancies and is a leading cause of perinatal mortality, preterm birth, and maternal morbidity (1). Through positive effects on vascular tone and glomerular capillary health, vascular endothelial growth factor (VEGF) and placental growth factor (PGF) are necessary for normal pregnancy (2–4). In PE, these proteins are antagonized by excessive placental production of soluble fms-like tyrosine kinase-1 (sFLT1), a splice variant of the VEGF receptor (2, 3), and in later pregnancy, by soluble endoglin (sENG), a soluble form of a transforming growth factor beta (TGFB1) receptor that prevents binding of TGFB1 to membrane-bound endoglin (5). The report by Kumasawa et al. (6) in PNAS describes the use of a mouse model in which placenta-specific expression of human sFLT1 is present from the time of implantation. The model faithfully reproduces many of the human findings of late-onset PE. The investigators also show that the lipid-lowering drug, pravastatin, ameliorates sFLT1-induced PE in these sFLT mice (6).

LUTEAL SUPPORT WITH INTRAVAGINAL PROGESTERONE INCREASES CLINICAL PREGNANCY RATES IN WOMEN WITH POLYCYSTIC OVARY SYNDROME USING LETROZOLE FOR OVULATION INDUCTION

OBJECTIVE To determine the effect of intravaginal micronized P on pregnancy rates in clomiphene citrate and letrozole ovulation induction cycles in women with polycystic ovary syndrome (PCOS). DESIGN Retrospective chart review. SETTING University-based assisted reproductive technology program. PATIENTS Women with PCOS who underwent ovulation induction with either clomiphene citrate (n = 90) or letrozole (n = 31) from January 2002 to December 2008. INTERVENTION(S) Clomiphene citrate (50-250 mg x 5 days) or letrozole (5 mg x 5 days) were used for ovulation induction. After either intercourse or IUI, patients received intravaginal micronized P (200 mg twice daily) according to prescribing physician preference. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate. RESULT(S) In clomiphene cycles, clinical pregnancies were documented in 15.3% of cycles (19 of 124) in the P group, compared with 12.1% (11 of 91) of the non-P group. In letrozole cycles, clinical pregnancies were documented in 21.1% of cycles (8 of 38) in the P group, compared with none (0 of 13) in the non-P group. CONCLUSION(S) Women with PCOS who used letrozole for ovulation induction had higher clinical pregnancy rates when using intravaginal P support. Luteal supplementation with P should be strongly considered in women with PCOS, especially in those using letrozole for ovulation induction.

HYPEROSMOLAR GLUCOSE INJECTION FOR THE TREATMENT OF HETEROTOPIC OVARIAN PREGNANCY

BACKGROUND: Heterotopic pregnancy describes the relatively rare coexistence of one or more intrauterine gestations and one or more extrauterine (ectopic) gestations. We describe a unique clinical case involving successful treatment of an ovarian heterotopic pregnancy through gestational sac aspiration and injection of hyperosmolar glucose. CASE: A 31-year-old woman presented with an ovarian ectopic pregnancy and a viable intrauterine pregnancy after ovulation induction with oral medications. The ovarian gestational sac was aspirated and then injected transvaginally with a small volume of 50% glucose in water. The ectopic pregnancy resolved, and the intrauterine pregnancy was delivered at term without complication. CONCLUSION: Gestational sac aspiration and injection of hyperosmolar glucose into an ovarian ectopic pregnancy was simple and efficacious without compromising a coexisting intrauterine pregnancy.

Supervised short-term nutrition and exercise promotes weight loss in overweight and obese patients with polycystic ovary syndrome

Thirty-two mid-reproductive-aged overweight and obese patients with polycystic ovary syndrome, most of whom had never exercised regularly, lost 3% to 4% of baseline weight, body mass index, and circumference of waist and hip while participating for 8.8 +/- 2.7 weeks in a medically supervised fitness program.

Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome

CONTEXT Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. OBJECTIVE We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. DESIGN This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004. SETTING This multi-center clinical trial was conducted in academic centers. PATIENTS Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. INTERVENTIONS Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. MAIN OUTCOME MEASURE The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. RESULTS Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, -14.7 to -21.3%) as well as creatinine (-4.2 to -6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (-10% in bilirubin, -9 to -11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. CONCLUSION Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.

Endometrial thickness predicts endometrial hyperplasia in patients with polycystic ovary syndrome

Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).

Follicle curetting at the time of oocyte retrieval increases the oocyte yield

PurposeTo determine whether follicle curetting at the time of oocyte retrieval increases oocyte yield.MethodsRetrospective review of all patients who underwent oocyte retrieval from July 1, 2003 to June 30, 2005.Main outcome measureNumber of oocytes retrieved. Secondary outcome measures: retrieval time, number of cryopreserved embryos, pregnancy rates, and incidence of ovarian hyperstimulation syndrome.ResultsThere were no differences in patient demographics, antral follicle count, cycle stimulation characteristics, fertilization rates, embryo quantity or quality, embryo cryopreservation rates, clinical pregnancy rates, live birth rates, or ovarian hyperstimulation syndrome between the groups. Retrievals that utilized curetting took three minutes longer. Follicle curetting significantly increased the number of oocytes retrieved, 13.9 ± 0.6 compared to 11.4 ± 0.6 oocytes without curetting (P = 0.003). The quantity of mature oocytes was also increased with curetting (10.3 ± 0.5 versus 8.4 ± 0.5, P = 0.006).ConclusionsThis study demonstrated that follicle curetting significantly increased oocyte yield. While it did not increase live birth rates, this increase in oocyte yield should lead to increased numbers of embryos for selection at transfer and increased embryos for cryopreservation.