To treat or not to treat: perceptions of the initial American Society for Reproductive Medicine COVID-19 recommendations among women's health providers.

PURPOSE: The objective of this study was to evaluate the perception of the initial ASRM COVID-19 recommendations for infertility treatment held by women's health providers within varying subspecialties, as well as their attitudes toward pregnancy and fertility during this time. METHODS: An electronic survey was sent to all women's healthcare providers, including physicians, mid-level providers and nurses, in all subspecialties of obstetrics and gynaecology (Ob/Gyn) at a large tertiary care university-affiliated hospital. RESULTS: Of the 278 eligible providers, the survey response rate was 45% (n = 127). Participants represented 8 Ob/Gyn subspecialties and all professional levels. Participants age 18-30 years were significantly more likely to feel that women should have access to infertility treatment despite the burden level of COVID-19 in respective community/states (p = 0.0058). Participants within the subspecialties of general Ob/Gyn, maternal foetal medicine and gynecologic oncology were significantly more likely to disagree that all women should refrain from planned conception during the COVID-19 pandemic, in comparison to those in urogynecology and reproductive endocrinology and infertility (p = 0.0003). CONCLUSIONS: Considering the immediate and unknown long-term impact of the COVID-19 pandemic on fertility care delivery, a better understanding of perceptions regarding infertility management during this time is important. Our study shows overall support for the initial ASRM recommendations, representing a wide spectrum of women's health providers.

Mitochondria in Ovarian Aging and Reproductive Longevity.

Mitochondrial dysfunction is one of the hallmarks of aging. Consistently mitochondrial DNA (mtDNA) copy number and function decline with age in various tissues. There is increasing evidence to support that mitochondrial dysfunction drives ovarian aging. A decreased mtDNA copy number is also reported during ovarian aging. However, the mitochondrial mechanisms contributing to ovarian aging and infertility are not fully understood. Additionally, investigations into mitochondrial therapies to rejuvenate oocyte quality, select viable embryos and improve mitochondrial function may help enhance fertility or extend reproductive longevity in the future. These therapies include the use of mitochondrial replacement techniques, quantification of mtDNA copy number, and various pharmacologic and lifestyle measures. This review aims to describe the key evidence and current knowledge of the role of mitochondria in ovarian aging and identify the emerging potential options for therapy to extend reproductive longevity and improve fertility.

Hysteroscopic Endometrial Polypectomy with Manual Vacuum Aspiration Compared to Mechanical Morcellation.

STUDY OBJECTIVE: To examine the effectiveness of hysteroscopy plus manual vacuum aspiration (MVA) for endometrial polypectomy compared with hysteroscopic morcellation. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Duke University Medical Center database. PATIENTS: Women who underwent hysteroscopic removal of endometrial polyps performed by Duke Fertility Center faculty physicians between January 1, 2015, and January 29, 2018, using either hysteroscopy plus MVA or hysteroscopic morcellation. INTERVENTIONS: The 2 groups were compared using the χ2 or Fisher's exact test, Student's t test, and multivariable regression analysis. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the duration of the procedure. Secondary outcomes were fluid deficit, rate of complete polyp resection, estimated blood loss, and operative complications. A total of 102 women undergoing endometrial polypectomy were identified. Patients in whom polyps were removed using only a hysteroscopic grasper and/or scissors (n = 31); patients who underwent an additional simultaneous procedure, such as laparoscopy (n = 12); and patients in whom the duration of the procedure was not recorded (n = 2) were excluded. Among the remaining 57 patients, 28 underwent hysteroscopy plus MVA and 29 underwent hysteroscopic morcellation. The mean duration of procedure was longer for hysteroscopic morcellation compared with hysteroscopy plus MVA (32 ± 10 minutes vs 20 ± 6 minutes; p = .04), and this difference remained significant after adjusting for age, body mass index, surgeon, and number and size of polyps. Mean fluid deficit was greater for morcellation than for hysteroscopy plus MVA (277 ± 204 mL vs 51 ± 97 mL; p < .001). Complete polyp resection was possible in all patients; however, the use of a hysteroscopic scissors and grasper was required for 1 patient in the MVA group. Estimated blood loss was minimal in all cases, and there were no operative complications. CONCLUSION: Hysteroscopy plus MVA is an effective method for removing large or multiple endometrial polyps, with outcomes comparable to hysteroscopic morcellation.

Fertility and Ovarian Reserve among Women with Rheumatoid Arthritis.

OBJECTIVE: We sought to identify causes for infertility in women with and without rheumatoid arthritis (RA). METHODS: Women with RA were matched to healthy controls. Differences in anti-Müllerian hormone (AMH) and anovulation were analyzed. RESULTS: Women with RA had lower AMH (ß -1.05, 95% CI -2.09 to -0.005), but no difference was observed when AMH was log-transformed. No difference in anovulation was observed. Infertility prevalence was similar between groups, primarily attributable to polycystic ovary syndrome in healthy controls but largely unexplained in women with RA. CONCLUSION: AMH was lower in women with RA, but reasons for infertility among women with RA remain unknown.

The Effect of Age and Body Mass Index on the Surgical Anatomy of Supraumbilical Port Insertion: Implications for Laparoscopic and Robotic Surgery.

BACKGROUND: Minimally invasive surgery is the preferred approach for performing many gynecologic procedures. Occasionally, supraumbilical port placement may be preferable to optimize visibility and maneuverability although the risks of complications are less well characterized compared to umbilical entry. METHODS: We conducted a retrospective review of computed tomograms from 92 patients to evaluate the anatomic considerations for umbilical and supraumbilical port entry based on patient age, body mass index (BMI), parity, abdominal wall thickness, and distance to the great vessels. RESULTS: Supraumbilical entry was not associated with differences in distance to the great vessels compared to the umbilicus. However, supraumbilical location and BMI were associated with greater abdominal wall thickness. Age and BMI were associated with greater distance to the great vessels, while age was associated with thinner abdominal wall. Multiple linear regression confirmed independent effects of age and BMI. No association between parity and distance to retroperitoneal vessels was observed. CONCLUSION: Younger patients may be at increased risk for great vessel injury and pre-peritoneal insufflation. Obese patients may be at risk for pre-peritoneal insufflation, while patients with BMI < 30, particularly with a skin-to-aorta distance < 7 cm, may be at an increased risk for great vessel injury. Surgeons should consider these factors when considering supraumbilical port entry.

Clinical, Hormonal, and Metabolic Parameters in Women with Subclinical Hypothyroidism and Polycystic Ovary Syndrome: A Cross-Sectional Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women, yet its clinical presentation shares similarities with several other endocrine disorders such as thyroid disease. Hence, the objective of this study was to further evaluate this association by investigating the clinical, hormonal, and metabolic parameters between subclinical hypothyroidism (SCH) and PCOS. METHODS: This is a cross-sectional study conducted in a tertiary care clinic at Cleveland, Ohio, USA. A total of 137 women diagnosed with PCOS by Rotterdam criteria were examined. SCH was defined as thyroid-stimulating hormone >2.5 mIU/L in the absence of symptoms of overt hypothyroidism. The mean age, body mass index (BMI), fasting plasma glucose (FPG), glucose tolerance test, hemoglobin A1c, fasting insulin, a 2 hours insulin level after 75 g glucose load, cholesterol, LDL, HDL, and homeostatic model assessment (HOMA) were compared between women with and without SCH. Logistic regression was used to adjust for age and BMI. RESULTS: Among 137 women with PCOS, 21.9% had SCH. Comparison groups were similar in both age and BMI and there was no difference in the mean values of all endocrine and metabolic parameters tested. However, abnormal FPG levels (OR 3.01; CI: 1.12-8.07. p = 0.03) and abnormal HOMA (OR 3.7; CI: 1.14-12.00. p = 0.03) were more likely in women who had SCH than in women without SCH independent of age and BMI. CONCLUSIONS: Women with PCOS and SCH are more likely to have impaired FPG values and impaired insulin sensitivity even after adjusting for age and BMI. Hence, close monitoring of PCOS patients for SCH may be beneficial.

What Is New in Minimally Invasive Surgery?: Best Articles From the Past Year.

Minimally invasive hysterectomy has a number of well-documented advantages compared with open hysterectomy, including lower complication rates, lower cost, and faster recovery. In this retrospective study of almost 10,000 women undergoing minimally invasive hysterectomy for endometrial cancer, the investigators found that laparoscopic compared with open hysterectomy was associated with a decreased risk of venous thromboembolism (0.7% vs. 2.2%, respectively; P<.001). This relationship remained after correcting for age, body mass index, race, operative time, comorbidity index, and surgical complexity. It was assumed that the majority of these patients undergoing surgery for cancer received some form of venous thromboembolism prophylaxis.

State Insurance Mandates and Multiple Birth Rates After In Vitro Fertilization.

OBJECTIVE: To examine the association between state-mandated insurance coverage for in vitro fertilization (IVF) and the incidence of multiple birth while controlling for differences in baseline patient characteristics. METHODS: We conducted a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System from 2007 to 2011 to examine the association between state-mandated insurance coverage for IVF and the incidence of multiple birth while controlling for differences in baseline patient characteristics. Analyses were stratified according to patient age and day of embryo transfer (3 or 5). RESULTS: Of the 173,968 cycles included in the analysis, 45,011 (25.9%) were performed in mandated states and 128,957 (74.1%) in nonmandated states. The multiple birth rate was significantly lower in mandated states (29.0% compared with 32.8%, adjusted odds ratio [OR] 0.87, 99.95% confidence interval [CI] 0.80-0.94). After stratification, this association remained statistically significant only in women younger than 35 years old who underwent transfer on day 5 (33.1% compared with 38.6%, adjusted OR 0.81, 99.95% CI 0.71-0.92). Among women younger than 35 years with day 5 transfer, the elective single embryo transfer rate was significantly higher in mandated states (21.8% compared with 13.1%, adjusted OR 2.36, 99.95% CI 2.09-2.67). CONCLUSION: State-mandated insurance coverage for IVF is associated with decreased odds of multiple birth. This relationship is driven by increased use of elective single embryo transfer among young women undergoing day 5 transfer.

Modified Open Laparoscopy Using a 5-mm Laparoscope.

BACKGROUND: In an effort to minimize injuries associated with closed laparoscopic entry, many surgeons use a 10-mm standard open laparoscopy technique. Disadvantages of this open technique are that it requires a larger incision, fascial sutures, and does not always achieve an airtight seal. Although 5-mm laparoscopics with excellent optics are available, little has been written about open techniques using them. TECHNIQUE: We report a modified 5-mm open laparoscopy technique without fascial sutures. The fascia is elevated with small Kocher forceps and incised in the midline. The peritoneum is bluntly perforated with a hemostat-directed cephalad, and a blunt trocar with a sleeve is inserted in this direction. After rotating the sleeve toward the pelvis, a 5-mm laparoscope is placed into the abdomen before insufflation. EXPERIENCE: We have performed approximately 350 laparoscopies with only one major complication of a perforated transverse colon densely adherent beneath the umbilicus in a woman without previous abdominal surgery. Minor carbon dioxide leakage was uncommon and no wound infections or hernias occurred. CONCLUSION: This 5-mm modified open laparoscopic entry technique minimizes some of the disadvantages associated with conventional open and closed 10-mm laparoscopic techniques while avoiding blind placement of sharp instruments into the peritoneal cavity.

Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone Control, and Implications for Pathophysiology.

Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.

Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants.

BACKGROUND: Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis. METHODS: This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively. RESULTS: The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis. CONCLUSIONS: Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis.

Does progesterone supplementation improve pregnancy rates in clomiphene citrate and intrauterine insemination treatment cycles?

AIM: To investigate the effect of empiric use of luteal phase progesterone supplementation to improve endometrial receptivity in women undergoing treatment with clomiphene citrate in combination with intrauterine insemination (CC-IUI). DESIGN: Retrospective cohort analysis. SETTING: University fertility center. PATIENTS: 426 CC-IUI cycles from 292 patients with unexplained infertility. INTERVENTIONS: Patients were treated with micronized intravaginal progesterone 100 mg twice daily beginning approximately three days after CC-IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy per initiated cycle as defined by presence of fetal heart rate on ultrasound. RESULTS: Clinical pregnancy rate was higher in patients receiving luteal phase support compared to patients not receiving luteal phase support (odds ratio: 2.04; 95% confidence interval: 1.01-4.14) after adjusting for all factors in the analysis using a multivariate logistic regression model. Age at the start of the cycle, BMI and CC dose were not shown to have an effect on clinical pregnancy rates. Patients with endometrial lining (EML) thickness 6-8 mm and >8 mm had increased clinical pregnancy rates compared to EML <6 mm independent of luteal phase progesterone use. Patients who appear to receive the greatest benefit of progesterone supplementation are in the 6-8 mm EML cohort. CONCLUSIONS: Luteal phase progesterone supplementation in CC-IUI cycles can improve endometrial receptivity as judged by the improved clinical pregnancy rates as the primary outcome.

Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome.

The object of this retrospective cohort study was to determine if hCG levels correlate with ovarian hyperstimulation syndrome (OHSS) risk after adjustment for other risk factors during in vitro fertilization (IVF). We measured serum hCG approximately 12 h after hCG trigger in women undergoing 406 cycles of controlled ovarian hyperstimulation for IVF between June 2006 and December 2009. Serum hCG levels were measured 12 h after trigger. Bivariate logistic regression was used to assess the association between patient and cycle characteristics and OHSS. In our series, mild to moderate OHSS occurred in 9% (38/406), and severe OHSS diagnosed in 1.5% (6/406) of IVF cycles. OHSS risk was increased in younger women (<30 years old: adjusted odds ratio: aOR 2.46, 95% confidence interval: CI 1.14-5.34), increased number of oocytes (11-20: aOR 6.79, 95% CI 1.97-23.40; >20: aOR 17.55, 95% CI 4.84-63.70), and increase E2 levels (≥3,000 pg/mL: aOR 2.59, 95% CI 1.33-5.05), but was unrelated to hCG level (100-200 IU/L: aOR 1.53, 95% CI 0.60-3.91; ≥200 IU/L: aOR 1.42 95% CI 0.48-4.20). These results indicate that OHSS risk during IVF is unrelated to serum hCG level measured approximately 12 h after trigger.

What is new in intrauterine devices? Best articles from the past year.

This month, we focus on current research about intrauterine devices. Dr. Hurd discusses four recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

Diagnosis and management of endometrial hyperplasia.

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.

Polycystic ovary syndrome and diabetes screening: a survey of gynecologists and reproductive endocrinologists.

OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are at high risk of developing type 2 diabetes mellitus. The purpose of this study was to assess self-reported methods used by specialists in obstetrics and gynecology (OB/GYN) and in reproductive endocrinology and infertility (REI) to screen for type 2 diabetes in women with PCOS. STUDY DESIGN: We analyzed responses to a web-based survey of from 123 OB/GYN and 223 REI physician members of the American Society for Reproductive Medicine. RESULTS: Initial diabetes screening of all women with PCOS was performed by fewer OB/GYNs (57%) than REIs (71%). Approximately 1/3 of both groups reported initial screening only for those with additional risk factors, and 3% reported no screening. Re-screening for diabetes was reportedly performed by similar numbers of OB/GYNs (49%) and REIs (53%). Re-screening was reportedly not performed by the remaining 51% of OB/GYNs and 47% of REIs. For initial screening, the 2h glucose tolerance test (GTT) was reportedly used by fewer OB/GYNs than REIs (59% vs 72%), fasting plasma glucose (FPG) by more OB/GYNs (22% vs 8%), and hemoglobin A1c (HbA1c) by a similar number (19% vs 20%). For re-screening, GTT was reportedly used by a similar proportion of OB/GYNs and REIs (27% vs 32%), FPG was used more by OB/GYNs (43% vs 23%), and HbA1c was used less (30% vs 45%). CONCLUSIONS: Not all OB/GYN and REI respondents followed diabetes screening guidelines for women with PCOS. Screening rates for women with PCOS might be increased by continued educational efforts concerning their high risk for diabetes, and by the recent recommendation to use HbA1c for diabetes screening in high-risk populations.