Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.

OBJECTIVE: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated center. PATIENT(S): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle. INTERVENTION(S): Ovulation induction, hCG trigger, and IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size. RESULT(S): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89. CONCLUSION(S): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility.

Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures.

The activation, growth, and maturation of oocytes to an ovulatory phase, termed folliculogenesis, is governed by the orchestrated activity of multiple specialized cell types within the ovary; yet, the mechanisms governing diversification and behavior of discrete cellular sub-populations within follicles are poorly understood. We use bulk and single-cell RNA sequencing to distinguish the transcriptional signature of prospectively isolated granulosa and theca/stroma cell subsets within human antral follicles derived from xenografts or ovaries. The analysis deconstructs phenotypic diversification within small (<4 mm) antral follicles, identifying secreted factors that are differentially enriched between mural and oophorus granulosa cells, and segregating stromal/support and steroidal activity between theca externa and interna, respectively. Multiple factors are differentially expressed in follicles of xenograft versus ovarian origin. These data capture a high-resolution transcriptional signature of granulosa and theca subpopulations and provide a systems-level portrait of cellular diversification in early antral human follicles.

Fresh or Frozen Embryo Transfer in In Vitro Fertilization: An Update.

The past decade has witnessed a rapid increase in the number of frozen-thawed embryo transfer (FET) cycles. Several factors have contributed to the increase in FET cycles, including improvement in culture media, vitrification, and an increase in preimplantation genetic testing of embryos. However, the accelerated trend in FET cycles also suggests that FET may be preferred over fresh embryo transfer. The current review explores the factors that have influenced this practice shift toward preferential FET and why this shift may be premature.

Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes.

The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included - 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P < 0.001) and total dosage of gonadotrophins administered (4095.5 versus 3155 IU; P < 0.001) was higher in the random-start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation.

Comparison of ovarian stimulation response in patients with breast cancer undergoing ovarian stimulation with letrozole and gonadotropins to patients undergoing ovarian stimulation with gonadotropins alone for elective cryopreservation of oocytes†.

The primary objective of this study is to compare the oocyte yield in breast cancer patients undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins with patients undergoing COS with standard gonadotropins for elective cryopreservation of oocytes. Odds ratios (OR) for the number of mature oocytes were estimated. Pregnancy outcomes for breast cancer patients undergoing frozen-thawed 2-PN embryo transfers (FETs) after oncologic treatment were also noted. 220 and 451 cycles were identified in the breast cancer and the elective cryopreservation groups, respectively. Patients in the former group had lower peak estradiol levels [464.5 (315.5-673.8) pg/mL] compared to the latter [1696 (1058-2393) pg/mL; p < 0.01]. More oocytes were retrieved in the breast cancer group (12.3 ± 3.99) compared to the elective cryopreservation group (10.9 ± 3.86; p < 0.01). The odds for mature oocytes with letrozole and gonadotropins was 2.71 (95% CI 1.29-5.72; p = 0.01). Fifty-six FETs occurred in the breast cancer group. The clinical pregnancy and live birth rates per FET cycle were 39.7%, and 32.3%, respectively. Our findings suggest that COS with letrozole and gonadotropins yield more mature oocytes at lower estradiol levels compared to COS with gonadotropins alone. Breast cancer patients undergoing FET after oncologic treatment have live birth rates comparable to age-matched counterparts.

Routine Monitoring of Liver, Renal, and Hematologic Tests After Single- or Double-Dose Methotrexate Treatment for Ectopic Pregnancies After In Vitro Fertilization.

STUDY OBJECTIVE: To investigate the trends in liver function tests (LFTs), renal function tests (RFTs), and complete blood count (CBC) between day 1 and day 7 after single- or double-dose methotrexate (MTX) treatment for sonographically confirmed ectopic pregnancies. DESIGN: Single center, retrospective chart review (Canadian Task Force classification II-3). SETTING: University-affiliated center. PATIENTS: All patients with a sonographically confirmed ectopic pregnancy after fresh in vitro fertilization-embryo transfer cycles between January 2004 and June 2013 treated with MTX were included. INTERVENTIONS: Single- or double-dose MTX treatment. MEASUREMENTS AND MAIN RESULTS: LFTs, specifically alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total bilirubin levels, were measured on day of MTX administration (baseline) and 7 days later (day 7). Similar measurements of RFTs (blood urea nitrogen [BUN] and creatinine) and CBC (white blood cell [WBC] and platelets) were also performed. The change in LFTs, RFTs, and CBC (Δ) between baseline and day 7 was calculated for both single- and double-dose MTX protocols. Furthermore, the change in LFTs, RFTs, and CBC (Δ baseline vs day 7) for single- and double-dose MTX protocols were compared. Complete data was available for 107 patients: 89 (83.2%) and 18 (16.8%) patients received single- and double-dose MTX treatment, respectively. For either single- or double-dose treatment, no significant difference was found between baseline and day 7 ALT, AST, albumin, total bilirubin, BUN, creatinine, WBC, or platelet levels after MTX treatment. A comparison of post-treatment changes in LFTs, RFTs, and CBC (Δ baseline vs day 7) also showed no difference between single- and double-dose protocols. CONCLUSION: Our study suggests that repeating LFTs, RFTs, or CBC on day 7 after single- or double-dose MTX treatment for sonographically confirmed ectopic pregnancies may not be necessary in patients with normal baseline testing on day 1.

Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine.

Despite different embryological origins, islet beta-cells and neurons share the expression of many genes and display multiple functional similarities. One shared gene product, vesicular monoamine transporter type 2 (VMAT2, also known as SLC18A2), is highly expressed in human beta-cells relative to other cells in the endocrine and exocrine pancreas. Recent reports suggest that the monoamine dopamine is an important paracrine and/or autocrine regulator of insulin release by beta-cells. Given the important role of VMAT2 in the economy of monoamines such as dopamine, we investigated the possible role of VMAT2 in insulin secretion and glucose metabolism. Using a VMAT2-specific antagonist, tetrabenazine (TBZ), we studied glucose homeostasis, insulin secretion both in vivo and ex vivo in cultures of purified rodent islets. During intraperitoneal glucose tolerance tests, control rats showed increased serum insulin concentrations and smaller glucose excursions relative to controls after a single intravenous dose of TBZ. One hour following TBZ administration we observed a significant depletion of total pancreas dopamine. Correspondingly, exogenous L-3,4-dihydroxyphenylalanine reversed the effects of TBZ on glucose clearance in vivo. In in vitro studies of rat islets, a significantly enhanced glucose-dependent insulin secretion was observed in the presence of dihydrotetrabenazine, the active metabolite of TBZ. Together, these data suggest that VMAT2 regulates in vivo glucose homeostasis and insulin production, most likely via its role in vesicular transport and storage of monoamines in beta-cells.