Larger oocyte cohorts maximize fresh IVF cycle birth rates and availability of surplus high-quality blastocysts for cryopreservation.

RESEARCH QUESTION: How does oocyte cohort size affect IVF treatment outcomes? DESIGN: Retrospective cohort analysis of 10,193 fresh autologous oocyte retrievals among good-prognosis patients <35 years from 2009 to 2015. The primary outcome was live birth from a fresh transfer; secondary outcomes included cumulative live birth potential from the retrieved cohort and frequency of severe ovarian hyperstimulation syndrome (OHSS). RESULTS: Live birth per fresh transfer increased as the oocyte cohort increased up to 11-15 oocytes, then plateaued. Beyond 15 oocytes, live birth rates from fresh transfer did not decrease, even at the highest oocyte yields. When accounting for the availability of cryopreserved high-quality supernumerary blastocysts, the cumulative number of potential live births per retrieval continued to increase as oocyte yield increased. Rates of severe OHSS increased rapidly with increasing cohort size above 7-10 oocytes when final oocyte maturation was triggered with human chorionic gonadotrophin (HCG), up to nearly 7% of HCG-triggered retrievals of >25 oocytes, but when triggered with gonadotrophin-releasing hormone (GnRH) agonist the severe OHSS rate remained relatively low and stable at approximately 1% even among retrievals of the largest oocyte cohorts. CONCLUSIONS: Live birth rates per fresh embryo transfer are highest among cycles with retrieval of 11 or more oocytes. Larger cohorts are not associated with any decline in fresh transfer birth rates. Total potential births per retrieval continue to increase as the number of retrieved oocytes increases. Rates of OHSS remain relatively low after retrieval of large oocyte cohorts if final maturation is triggered with GnRH agonist rather than HCG.

The impact of vitrification on murine germinal vesicle oocyte In vitro maturation and aurora kinase A protein expression.

PURPOSE: Investigate the effect of vitrification on in vitro maturation (IVM) and expression of Aurora kinases A, B, and C in germinal vesicle (GV)-stage oocytes. METHODS: GV-stage oocytes from B6D2F1 female mice 7-11 weeks of age were vitrified after collection, thawed, and matured in vitro for 0, 4, 8, and 12 h (hrs). The rate of germinal vesicle breakdown (GVBD), spindle apparatus assembly, and Aurora kinase mRNA and protein expression during IVM was measured. RESULTS: Oocyte vitrification was associated with significant delays in both GVBD and normal spindle apparatus assembly at 4 and 8 h of IVM (p < 0.05). There was no difference in mRNA levels between control and vitrified oocytes for any of the Aurora kinases. Aurora A protein levels were reduced in vitrified compared to control oocytes at 0 h (p = 0.008), and there was no difference at 4 and 8 h (p = 0.08 and 0.69, respectively) of IVM. CONCLUSIONS: Vitrified oocytes have delayed GVBD and normal spindle assembly during in vitro maturation. Reduced levels of Aurora A protein immediately post-thaw may be associated with the impaired oocyte maturation manifested by the delayed progression through meiosis I and II, and the atypical timing of the formation of meiotic spindles in vitrified GV-stage oocytes.

Fertility Preservation Before Deployment: Oocyte and Sperm Freezing in Members of the Active Duty Military.

Active duty military service and deployment has the potential to compromise fertility through combat-related genitourinary injury, gonadotoxic exposures, and physical separation from a partner. Despite a growing interest among the military community as well as promising efficacy and safety data, fertility preservation remains an uncovered benefit for active duty soldiers. In 2016, the Pentagon proposed a program that would cover oocyte and sperm cryopreservation for any member of the active duty military desiring its use. Regrettably, that funding was not secured and predeployment fertility preservation remains an out-of-pocket expense. Today, advocacy groups, non-for-profit organizations, and physicians remain vigilant in their attempts to drive another government initiative through Congress. While activism continues, it is important to stress the value of fertility preservation counseling in soldiers' predeployment preparation and military family planning.

Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval.

OBJECTIVE: To evaluate a single treatment center's experience with autologous IVF using vitrified and warmed oocytes, including fertilization, embryonic development, pregnancy, and birth outcomes, and to estimate the likelihood of live birth of at least one, two, or three children according to the number of mature oocytes cryopreserved by elective fertility preservation patients. DESIGN: Retrospective cohort study. SETTING: Private practice clinic. PATIENT(S): Women undergoing autologous IVF treatment using vitrified and warmed oocytes. Indications for oocyte vitrification included elective fertility preservation, desire to limit the number of oocytes inseminated and embryos created, and lack of available sperm on the day of oocyte retrieval. INTERVENTION(S): Oocyte vitrification, warming, and subsequent IVF treatment. MAIN OUTCOME MEASURE(S): Post-warming survival, fertilization, implantation, clinical pregnancy, and live birth rates. RESULT(S): A total of 1,283 vitrified oocytes were warmed for 128 autologous IVF treatment cycles. Postthaw survival, fertilization, implantation, and birth rates were all comparable for the different oocyte cryopreservation indications; fertilization rates were also comparable to fresh autologous intracytoplasmic sperm injection cycles (70% vs. 72%). Implantation rates per embryo transferred (43% vs. 35%) and clinical pregnancy rates per transfer (57% vs. 44%) were significantly higher with vitrified-warmed compared with fresh oocytes. However, there was no statistically significant difference in live birth/ongoing pregnancy (39% vs. 35%). The overall vitrified-warmed oocyte to live born child efficiency was 6.4%. CONCLUSION(S): Treatment outcomes using autologous oocyte vitrification and warming are as good as cycles using fresh oocytes. These results are especially reassuring for infertile patients who must cryopreserve oocytes owing to unavailability of sperm or who wish to limit the number of oocytes inseminated. Age-associated estimates of oocyte to live-born child efficiencies are particularly useful in providing more explicit expectations regarding potential births for elective oocyte cryopreservation.

Hematometra in a patient with Cornelia De Lange syndrome.

BACKGROUND: Hematometra is usually the result of developmental anomalies or may be secondary to cervical obstruction. Abnormal uterine contractile function (atony) would be an uncommon cause of hematometra. CASE: An 18-year-old female with Cornelia De Lange syndrome and abdominal pain was found to have a hematometra on ultrasound examination. On pelvic examination, her cervical canal was patent and was easily dilated, but the hematometra did not drain until suprapubic pressure was applied. Two weeks postoperatively, pelvic magnetic resonance imaging showed a markedly thinned uterine myometrium and a recurrent hematometra, prompting the decision to perform a hysterectomy. CONCLUSION: Hematometra in a patient with Cornelia De Lange syndrome may be the result of abnormal uterine contractile function.

Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization.

OBJECTIVE: To assess the impact of elevated peak serum E(2) levels (EPE(2); defined as levels >90th percentile) on the day of hCG administration during controlled ovarian hyperstimulation (COH) for IVF on the likelihood for small for gestational age (SGA), preeclampsia (PreE), and preterm delivery (PTD) in singleton pregnancies. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): Singleton live-birth pregnancies conceived after fresh IVF-ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The delivery rate of SGA infants and the development of PreE and PTD in patients with and without EPE(2). RESULT(S): Patients with EPE(2) during COH were more likely to deliver SGA infants (7 [26.9%] vs. 10 [3.8%]; odds ratio [OR], 95% confidence interval [CI] {9.40, 3.22-27.46}) and develop PreE (5 [18.5%] vs. 12 [4.5%]; adjusted OR, 95% CI {4.79, 1.55-14.84}). No association was found between EPE(2) and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE(2) level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E(2) cutoff value of 3,450 pg/mL (>90th percentile level), the positive predictive value was 37%, while the negative predictive value was 92%. CONCLUSION(S): EPE(2) level (>3,450 pg/mL) on the day of hCG administration during COH is associated with greater odds of developing PreE and delivery of an SGA infant in singleton pregnancies resulting from IVF cycles.

Rescue human chorionic gonadotropin for false empty follicle syndrome: optimism for successful pregnancy outcome.

OBJECTIVE: To describe two cases of successful pregnancy after a rescue course of hCG in the setting of false empty follicle syndrome. DESIGN: Case report. SETTING: Academic medical center. PATIENT(S): Two patients undergoing ultrasound-guided oocyte retrieval with failure to obtain oocytes during oocyte retrieval. INTERVENTION(S): Rescue course of hCG with second oocyte retrieval 35 hours later. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Two live-birth pregnancies. CONCLUSION(S): Live-birth pregnancies are a realistic possibility after administration of a rescue course of hCG and repeat oocyte retrieval in the setting of false empty follicle syndrome.

Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation.

BACKGROUND: Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function. METHODS: We utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. RESULTS: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization (progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype. CONCLUSIONS: Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome with a single septate uterus: a novel anomaly and description of treatment options.

OBJECTIVE: To report a rare Mayer-Rokitansky-Kuster-Hauser (MRKH) anomaly with a septate midline uterus and describe management options. DESIGN: Case report. SETTING: Major academic medical center. PATIENT(S): Two adolescent patients presented with pelvic pain and primary amenorrhea. Radiographic imaging showed evidence of a bicornuate uterus with two uterine horns, cervical hypoplasia, and absence of the upper vagina. INTERVENTION(S): Owing to pain, both patients planned laparoscopy with bilateral hemihysterectomies, but in each case laparoscopy showed evidence of a single midline uterus. Continuous hormone therapy was used to suppress pain and retrograde menstruation. MAIN OUTCOME MEASURE(S): Uterine preservation and future fertility management. RESULT(S): Given the fertility potential, the treatment plan was to continue hormone therapy until adulthood, when the young woman could select a treatment option for herself. After 2 years, one patient elected hysterectomy at age 18.5 due to persistent pain, while the other patient continues uterine preservation. CONCLUSION(S): We present two cases of a rare and uniquely described anomaly of MRKH with a single septate midline uterus. We recommend uterine preservation until the age of 18, at which point the patient may select her treatment option. Novel options include septal resection with subsequent assisted reproductive technology (ART) and cesarean delivery or ART and a gestational carrier.

hMG increases the yield of mature oocytes and excellent-quality embryos in patients with a previous cycle having a high incidence of oocyte immaturity.

In a selected group of patients with >20% oocyte immaturity during an IVF cycle with FSH alone, the addition of hMG to the stimulation protocol results in a higher yield of mature oocytes and excellent-quality embryos.

Effect of endometrioma cyst fluid exposure on peritoneal adhesion formation in a rabbit model.

OBJECTIVE: To determine whether copious lavage and suction of human endometrioma fluid placed in the peritoneal cavity of rabbits reduces adhesion formation compared to no lavage. DESIGN: Prospective, randomized, blinded study. SETTING: Academic research environment. ANIMAL(S): Twenty-four female New Zealand white rabbits. INTERVENTION(S): Rabbits randomized into three groups: [1] laparoscopy with instillation of human endometrioma material, no lavage; [2] laparoscopy with instillation of human endometrioma material, followed by clearance of all visible endometrioma fluid by saline lavage and suction; [3] laparoscopy alone. MAIN OUTCOME MEASURE(S): Six weeks after laparoscopy, adhesions scored by laparotomy using standard visual assessment scoring system and histologic microscopic evaluation. Data evaluated using Kruskal-Wallis and median nonparametric tests. RESULT(S): For groups 1, 2, and 3, respectively, mean total clinical adhesion scores were 0.67 (95% confidence interval [CI] -0.87, 2.2), 3.67 (95% CI 1.27, 6.07), and 0 (95% CI 0, 0). Group 2 had statistically significantly higher mean adhesion scores compared to group 1. Histologic adhesion scores followed the trend of clinical adhesion scores. CONCLUSION(S): In this rabbit model, human endometrioma fluid exposure in the peritoneal cavity is not associated with adhesion formation. Instillation of endometrioma fluid followed by copious saline lavage is strongly associated with adhesion formation.