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Background: Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes. Methodology/Principal Findings: We retrieved data for all 1117 IVF cycles performed in 2005 at Stanford University Medical Center, and further analyzed clinical data from the 665 fresh IVF, non-donor cycles and their associated 4144 embryos. Thirty variables representing patient characteristics, clinical diagnoses, treatment protocol, and embryo parameters were analyzed in an unbiased manner by regression tree models, based on dichotomous pregnancy outcomes defined by positive serum β-human chorionic gonadotropin (β-hCG). IVF cycle outcomes were most accurately predicted at ∼70% by four nonredundant, embryo cohort-specific variables that, remarkably, were more informative than any measures of individual, transferred embryos: Total number of embryos, number of 8-cell embryos, rate (percentage) of cleavage arrest in the cohort and day 3 follicle stimulating hormone (FSH) level. While three of these variables captured the effects of other significant variables, only the rate of cleavage arrest was independent of any known variables. Conclusions/Significance: Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort. [ABSTRACT FROM AUTHOR]

Objective: Hyperandrogenic conditions in women are associated with increased rates of miscarriage. However, the specific role of maternal testosterone in early pregnancy and its association with pregnancy outcome is unknown. The purpose of this study was to compare serum testosterone levels during early pregnancy in women with and without polycystic ovary syndrome (PCOS) who either had successful pregnancies or miscarried., Method: We collected serum samples from women attending a university-based fertility centre at the time of their first positive serum beta human chorionic gonadotropin pregnancy test. The samples were subsequently assayed for total testosterone level. We used logistical regression modelling to control for PCOS diagnosis, BMI, and age., Results: Total testosterone levels were available for 346 pregnancies, including 286 successful pregnancies and 78 first trimester miscarriages. We found no difference in total testosterone levels between women who subsequently had an ongoing pregnancy (mean concentration 3.6 ± 2.6 nmol/L) and women with a miscarriage (mean 3.6 ± 2.4 nmol/L). Using the Rotterdam criteria to identify women with PCOS, we also found no differences in serum testosterone between women who had ongoing pregnancies or miscarriages, either with PCOS (P = 0.176) or without PCOS (P = 0.561)., Conclusions: Our findings show that early pregnancy testosterone levels do not predict pregnancy outcome, and they call into question the role of testosterone in causing miscarriage in populations of women with PCOS. Further research is needed to elucidate the normal progression of testosterone levels during pregnancy and to investigate further the relationship between PCOS and miscarriage.

Objective: To evaluate the pregnancy rate, ovarian responsiveness, and endometrial thickness in infertility patients with a history of methotrexate exposure who subsequently underwent controlled ovarian stimulation., Design: Retrospective cohort study., Setting: University reproductive endocrinology and infertility program., Subject(s): Forty-eight women with infertility undergoing ovarian stimulation after receiving methotrexate treatment for ectopic gestation., Intervention(s): Methotrexate administration and controlled ovarian stimulation., Main Outcome Measure(s): Pregnancy rate, cycle day 3 FSH levels, number of oocytes retrieved, and endometrial thickness., Result(s): The cumulative intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2 years after methotrexate exposure was 43%, with a mean time to conceive of 181 days. Thirty-five patients with similar fertility treatments pre- and post-methotrexate were identified. Within this group, when an IVF cycle occurred within 180 days of methotrexate exposure, a significant decline in oocytes retrieved was observed. Cycles performed later than 180 days after methotrexate exposure did not exhibit a decrease in oocyte production. Endometrial development was similar at all time points examined., Conclusion(s): These findings suggest a time-limited and reversible impact of methotrexate on oocyte yield. If confirmed by larger clinical series and/or animal data, these results may impact the management of ectopic gestation in the patient with a history of infertility or the timing of subsequent treatments.

Objective: To evaluate obstetric complications in women who conceived through donated oocytes compared with women who conceived through assisted reproduction using autologous oocytes., Design: Retrospective cohort analysis., Setting: Stanford Hospital and Clinics and Lucille Packard Children's hospital, both tertiary referral centers., Patient(s): A cohort of 71 oocyte recipients who underwent in vitro fertilization (IVF) were compared to all women over 38 years who conceived through IVF with autologous oocytes (n = 108) between January 1, 2001, and December 31, 2005, at Stanford University and subsequently delivered infants at Lucille Packard Children's Hospital., Intervention(s): Assisted reproductive technology with donor oocytes., Main Outcome Measure(s): Obstetric charts of the donor-oocyte recipients were compared for all women over 38 years old who had conceived through IVF with autologous oocytes at the same center (n = 108) and delivered at the same hospital during the same time period. Perinatal complications including preeclampsia, diabetes, preterm labor, preterm premature rupture of membranes and placental abnormalities, mode of delivery, presentation, Apgar scores, gestational age at delivery, and weight were compared between the groups., Result(s): Oocyte recipients and autologous oocyte controls had similar rates of complications of prematurity, hypertensive disorders of pregnancy, gestational diabetes, and placental abnormalities. Infant birth weights and gestational age at time of delivery were similar between the two groups., Conclusion(s): This study suggests that women undergoing IVF with donor oocytes are not at increased risk for complications during pregnancy or at increased immediate neonatal complications compared with women of advanced maternal age undergoing IVF with autologous oocytes.