The effects of irisin and leptin on steroidogenic enzyme gene expression in human granulosa cells: In vitro studies.

Reproduction and energy metabolism are closely related, and fertility can be directly affected by either obesity or malnutrition. In this study, we investigated the in vitro effects of irisin and leptin, two hormones primarily involved in energy metabolism, on the expression of genes encoding key steroidogenic enzymes in primary cultures of human granulosa cells. Granulosa cells were purified from follicular fluid samples obtained during in vitro fertilization (IVF) procedure, cultured, and treated with irisin (125-2000 ng/ml) or leptin (25-400 ng/ml) for 1-3 days. mRNA expression levels of cytochrome P450 enzymes [CYP11A1, CYP19A1, CYP21A2], hydroxy-delta-5-steroid dehydrogenase, 3 beta and steroid delta-isomerase 1 (HSD3B1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3) were measured using qRT-PCR analysis. Irisin significantly upregulated CYP19A1 mRNA levels, while leptin upregulated CYP19A1 and HSD3B1 mRNA levels. These preliminary results show that irisin and leptin may directly affect the expression of the genes important for ovarian steroidogenesis and female reproduction.

The impact of the COVID-19 pandemic on gestational carriers.

Reproductive medicine has been significantly impacted by the coronavirus (COVID-19) pandemic, and this includes the gestational carrier (GC) process. The objectives of this commentary are to evaluate the impact of COVID-19 on the GC process, as well to communicate Shady Grove Fertility's considerations of and response to COVID-19 on the GC process to the larger assisted reproductive technology (ART) community. We also gathered conclusions drawn from available data on the impact of COVID-19 infection on maternal and neonatal morbidity and mortality as well as on counseling patients on vaccination. We compiled proposals to mitigate risk and to maximize safe evaluation and treatment for GCs during the ongoing pandemic. Over 2 years after the onset of the pandemic, the multiple resurgences of cases in the USA have necessitated nimble strategies to provide ongoing and safe reproductive care and have posed unique challenges to the GC process. With the prospect of the virus continuing to spread globally well into the future, as healthcare professionals of the ART community, we will need to ensure effective collaboration and communication as we provide care during the ongoing pandemic.

In vitro treatment of human granulosa cells with irisin and leptin: Quantitative RT-PCR array data (female infertility panel).

Reproduction is closely related to energy metabolism: physical activity and adiposity (either insufficient weight or obesity) can affect female fertility. Irisin is a myo- and adipokine produced by skeletal muscles during exercise or shivering as well as in smaller amounts by subcutaneous visceral adipocytes [1]. Leptin is a neuroendocrine adipokine regulating satiety and energy expenditure. Circulating levels of both, irisin and leptin, correlate with adiposity status and physical activity [2], [3], [4], [5], [6]. This article presents data from quantitative PCR array of the in vitro effects of irisin and leptin on cultured human ovarian granulosa cells. Granulosa cells were purified from follicular fluid samples obtained from women undergoing in vitro fertilization (IVF) procedure and were subjected to treatment with irisin (500 ng/mL) or leptin (100 ng/mL) for 24 h. The array included 84 genes involved in female fertility.

The impact of preimplantation genetic testing on prenatal diagnostic procedures.

OBJECTIVE: In recent years, cell-free DNA screening has significantly reduced the number of invasive prenatal diagnostic testing in pregnancy. Preimplantation genetic testing for aneuploidies (PGT-A) is a commonly performed screening test in in vitro fertilization (IVF) pregnancies. Therefore, we aimed to determine the impact of PGT-A on subsequent utilization of prenatal diagnostic testing in IVF pregnancies. METHODS: Retrospective cohort of singleton and twin IVF pregnancies at a single center from January 2014 to December 2017. The rate of invasive diagnostic genetic testing (chorionic villus sampling (CVS) and/or amniocentesis) was compared between patients with pregnancies achieved after transfer of a euploid embryo by PGT-A (n = 71) and those with pregnancies achieved after transfer of an untested embryo (n = 38). Wilcoxon rank sum and Fisher's exact tests were used for statistical analysis. RESULTS: There was no statistically significant difference in the number of prenatal diagnostic procedures (25.4% PGT-A euploid embryo versus 31.6% untested embryo, p = .51 and p = .32 for one-sided and two-sided analyses, respectively) between the two groups. Maternal age, nuchal translucency measurements and the rate of abnormal sonographic findings were similar between the two groups. Patients without PGT-A pregnancies had a higher BMI (mean 29.6, p = .01) and were ethnically different (p = .013) compared to those with PGT-A. CONCLUSION: The implementation of PGT-A in IVF patients did not reduce the number of invasive diagnostic tests performed at our institution.

Vaginal cuff dehiscence following controlled ovarian stimulation recognized during egg retrieval.

BACKGROUND: Vaginal cuff dehiscence is a rare complication of hysterectomy. Those who choose to undergo controlled ovarian stimulation (COS) and oocyte cryopreservation following hysterectomy must be aware that elevated abdominal pressure from stimulation as well as transvaginal ultrasound use during monitoring may increase the risk of cuff dehiscence. CASE: We present a case of a 25-year-old patient who had undergone a hysterectomy four months prior for endometrial cancer who was found to have vaginal cuff dehiscence which was recognized at the time of egg retrieval after COS. Prompt recognition and appropriate management led to successful treatment. CONCLUSION: Patients presenting for oocyte cryopreservation following hysterectomy are at risk for cuff dehiscence. Providers should allow ample time for proper cuff healing prior to COS and oocyte cryopreservation.

Choosing an expanded carrier screening panel: comparing two panels at a single fertility centre.

RESEARCH QUESTION: What are the factors contributing to similarities and differences in carrier rates between two expanded carrier screening (ECS) panels? DESIGN: Retrospective cross-sectional study. A total of 7700 infertility patients who underwent ECS from one of two genetic testing laboratories (Panel A or Panel B) using a genotyping microarray were included in the study. Individuals presenting to the Centre between June 2013 and July 2015 underwent screening via Panel A. Those presenting between August 2015 and April 2017 underwent screening via Panel B. Self-reported ethnicity was recorded. Panel content, carrier rates for the overall study population and for comparable self-reported ethnicities, carrier couple rates, and the top 10 identified disorders were compared. RESULTS: Of 4232 individuals screened by Panel A, 1243 were identified as carriers (29.4%). Panel B identified 1503 carriers among the 3468 (43.3%) participants (P < 0.0001). Carrier couple rate also varied between panels (1.2% versus 3.1%; P = 0.0017). A total of 311 disorders covering 2746 mutations were observed across the two ECS panels, with 372 (13.5%) shared mutations. Carrier rates did not differ for the shared mutations overall and across ethnicities. Significant differences were observed when comparing unique content in the overall population (P < 2 .2 × 10-16) and across ethnicities (P < 2.2 × 10-16 to 0.0010). CONCLUSIONS: Carrier rates in the overall population and across ethnicities vary widely based on panel content, and highlight the need to expand panel content as well as incorporate preconception carrier screening coupled with genetic counselling into routine assisted reproduction practice.

Comparing ethnicity-based and expanded carrier screening methods at a single fertility center reveals significant differences in carrier rates and carrier couple rates.

PURPOSE: To evaluate the efficiency of expanded carrier screening (ECS) compared with ethnicity-based screening in identifying carriers. METHODS: A total of 4232 infertility patients underwent ECS from a single genetic testing laboratory at our center between June 2013 and July 2015. Self-reported ethnicity was recorded. Carrier rates based on ECS were calculated. In addition, carrier status was determined for two other screening panels: ethnicity-based guidelines or the ECS panel recommended by the American College of Obstetricians and Gynecologists (ACOG) using ECS results. Carrier rate and carrier couple rates were compared in the overall study population and in each self-reported ethnicity. RESULTS: The ECS panel used to screen the patient population identified 1243 carriers (29.4%). For the same population, ethnicity-based screening and the ACOG panel would have identified 359 (8.5%) and 659 carriers (15.6%), respectively, representing statistically significant differences. Differences in identifying carriers across self-reported ethnicities varied. In 15 couples (1.2%), both partners carried pathogenic variants for the same genes, 47% of whom would have been missed had screening been ethnicity-based. CONCLUSION: We propose that all reproductive-aged women should be offered ECS. Carrier couple rates would likely increase further with expansion of the panel, playing a pivotal role in preventing genetic disease in fertility clinics.

Reduction in the number of CGG repeats on the FMR1 gene in carriers of genetic disorders versus noncarriers.

OBJECTIVE: CGG repeat expansion on the fragile X mental retardation 1 (FMR1) gene is used to diagnose fragile X syndrome. Previous studies have discussed the correlation between the number of CGG repeats and its associated phenotypic components. The objective of this study is to determine whether the number of CGG repeats differ between carriers of genetic disorders versus noncarriers. METHODS: We performed a retrospective chart review of 2867 patients who received genetic screening at our fertility clinic between June 2013 and July 2015. The number of CGG repeats on allele 1 and allele 2 on the FMR1 gene was collected and it was specified whether the patient was a carrier or a noncarrier of a specific mutation. Patients with CGG repeats greater than or equal to 45 were excluded from the study. RESULTS: Carriers (n=759) had a reduced number of repeats compared to noncarriers (n=2024) on allele 1 (p=.03), allele 2 (p=.02) and the average of both alleles (p=.01). Additionally, the number of CGG repeats from the ten most carried diseases from the cohort were used and tested individually for clinical significance against the number of repeats in the noncarriers. A reduction in repeats was shown in several mutations and a few were outliers. CONCLUSION: Our results demonstrate that there is a significant reduction in the number of CGG repeats in carriers of genetic mutations. A larger scale study of disease carrying patients would be beneficial.

Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma.

OBJECTIVES: This study evaluated fertility and oncological outcomes in women with complex atypical hyperplasia (CAH) or nonmyoinvasive grade 1 endometrioid endometrial carcinoma (EM) who desired fertility-sparing therapy. STUDY DESIGN: The retrospective cohort study included women younger than 45 years with CAH or EM who desired fertility-sparing treatment at our institution. Only patients for whom both oncological treatment and pregnancy outcomes were available were included. Statistical analyses were performed using a Fisher exact test, Pearson χ(2) test, and Spearman rank correlation test, as appropriate. RESULTS: Seventy-five patients were identified, and 23 (13 CAH, 10 EM) met the inclusion criteria. All 23 patients had at least 1 prior pregnancy. Treatment was split between oral progesterone only (38.5% CAH, 40% EM), levonorgestrel intrauterine device only (30.8% CAH, 20% EM), and both (30.8% CAH, 40% EM). After a median follow-up of 13 months (range, 3-74 months), 9 patients (46.2% CAH, 30% EM, P = .39) had persistent/progressive disease. Eight patients (30.8% CAH, 40% EM, P = .69) ultimately had a hysterectomy, and 3 of these (13.0%) were found to have persistent/progressive disease. Median time from diagnosis to hysterectomy was 13 months (range, 4-56 months). Fourteen of the 23 patients utilized assisted reproductive techniques (60.9%); 12 underwent IVF and 2 chose a gestation carrier. Seven clinical intrauterine pregnancies (30.4%) resulting in 6 live births (26.1%) were found in the entire cohort. CONCLUSION: Fertility-sparing treatment for CAH and grade 1 endometrial cancer is feasible with progestin therapy and leads to clinically meaningful rates of pregnancy in young women who desire fertility.

Rare case of ovarian cystic lymphangioma.

Lymphangiomas are rare, generally benign tumors of the lymphatic system comprised of multiple cystic spaces lined with endothelium. Lymphangiomas may arise in any part of the body. Lymphangioma of the ovary is rare; we have identified only 13 reports in a 50-year literature survey (PubMed 1959-2009). Typically, lymphangiomas are slow-growing tumors that remain asymptomatic for a long time. They are most often found incidentally in abdominal or pelvic imaging studies or at surgery or autopsy. Wide excision of the lesion with microscopically clear margins is the best approach when feasible. A postmenopausal woman had a symptomatic pelvic mass. Imaging studies demonstrated a complex left ovarian cyst. Complete removal of a cystic lymphangioma was successfully performed at laparoscopy. Cystic lymphangiomas should be included in the differential diagnosis of an ovarian cystic mass, and laparoscopic excision may be the method of treatment.

Laparoscopic resection of endometriosis in a patient with a ventriculoperitoneal shunt using the LapDisc.

The surgical approach in a patient with a ventriculoperitoneal shunt in need of abdominal surgery remains controversial. The risk of increased intracranial pressure with pneumoperitoneum in laparoscopy is still unresolved. We used the LapDisc (Ethicon, Inc., Somerville, New Jersey) to access the shunt and temporarily seal it, which enabled us to perform laparoscopic resection of endometriosis without subjecting the shunt to high intraabdominal pressure. The benefits of this approach are the ability to perform laparoscopy, less skin-to-shunt contact minimizing infection, and elimination of possible increased intracranial pressure secondary to pneumoperitoneum. With the progress made in the management of hydrocephalus, patients with ventriculoperitoneal (VP) shunts enjoy a longer lifespan. Therefore, the gynecologic laparoscopic surgeon can expect to treat a patient with a VP shunt in place.

Correlation of antimüllerian hormone and baseline follicle-stimulating hormone levels.

OBJECTIVE: To compare how a given level of antimüllerian hormone (AMH) might be used to predict the level of FSH. DESIGN: Retrospective cohort study. SETTING: Academically affiliated private fertility center. PATIENT(S): Eighty-one women in preparation for an IVF cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of FSH and AMH before start of ovulation induction. RESULT(S): Serum AMH and log-converted FSH levels were negatively correlated (R(2) = 0.42). The linear regression model for FSH, based on random AMH, was as follows: LnFSH = 2.3 + -0.25 x lnAMH; 95% confidence limits of the coefficient 0.-32 to 0.-18, suggesting that an AMH level of 0.5 ng/mL is predictive of a baseline FSH level of 12.1 mIU/mL (95% confidence interval 11.4-12.7 mIU/mL). CONCLUSION(S): These data demonstrate a statistical association between FSH and AMH in assessing ovarian reserve. Using FSH and AMH in combination may improve the evaluation of ovarian reserve. However, it remains to be determined which of these two ovarian function parameters is superior in assessing ovarian reserve with a single test and which test, or combination of tests, will in the future be used in routine infertility evaluations.