Dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatment: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Dietary and/or physical activity interventions are often recommended for women with overweight or obesity as the first step prior to fertility treatment. However, randomised controlled trials (RCTs) so far have shown inconsistent results. Therefore, we propose this individual participant data meta-analysis (IPDMA) to evaluate the effectiveness and safety of dietary and/or physical activity interventions in women with infertility and overweight or obesity on reproductive, maternal and perinatal outcomes and to explore if there are subgroup(s) of women who benefit from each specific intervention or their combination (treatment-covariate interactions). METHODS AND ANALYSIS: We will include RCTs with dietary and/or physical activity interventions as core interventions prior to fertility treatment in women with infertility and overweight or obesity. The primary outcome will be live birth. We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials and trial registries to identify eligible studies. We will approach authors of eligible trials to contribute individual participant data (IPD). We will perform risk of bias assessments according to the Risk of Bias 2 tool and a random-effects IPDMA. We will then explore treatment-covariate interactions for important participant-level characteristics. ETHICS AND DISSEMINATION: Formal ethical approval for the project (Venus-IPD) was exempted by the medical ethics committee of the University Medical Center Groningen (METc code: 2021/563, date: 17 November 2021). Data transfer agreement will be obtained from each participating institute/hospital. Outcomes will be disseminated internationally through the collaborative group, conference presentations and peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42021266201.

Development of endometrial stromal sarcoma in a patient undergoing in vitro fertilization: A case report.

Development of endometrial stromal sarcoma during in vitro fertilization (IVF) is rare. We encountered a case of endometrial stromal sarcoma (ESS) presenting as a new endometrial mass in a patient undergoing donor egg IVF, despite normal imaging and exams prior to and throughout treatment. To our knowledge, this is the only report describing the rapid growth of ESS during IVF treatment. When diagnosing an endometrial stromal sarcoma, it is important for the clinician and patient to be aware that full histologic inspection is required to distinguish it from a benign neoplasm. Given the need for a hysterectomy for definitive diagnosis, this case presents ethical challenges and potential for patient distress.

Major depression, antidepressant use, and male and female fertility.

OBJECTIVE: To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments. DESIGN: Cohort study. SETTING: Clinics. PATIENT(S): Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility). INTERVENTION(S): Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD. MAIN OUTCOME MEASURE(S): Primary outcome: live birth. SECONDARY OUTCOMES: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS). RESULT(S): Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception. CONCLUSION(S): Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00719186 and NCT01044862.

Informing the development and uptake of a weight management intervention for preconception: a mixed-methods investigation of patient and provider perceptions.

BACKGROUND: It is recommended for women to have a healthy body mass index before conception. However, there is limited research on appropriate preconception interventions for weight loss. Furthermore, there is a lack of knowledge on providers' willingness to refer to particular behavioral interventions and the degree to which patients would attend those interventions. METHODS: A cross-section of 67 patients and 21 providers completed surveys related to their demographics and willingness to refer/attend a number of interventions for weight loss. A case study of three patients from the target audience was used to elicit detailed feedback on preconception weight status and weight loss intervention. RESULTS: Overall, patients were willing to attend a variety of interventions, regardless of BMI category. Focus group participants shared that weight loss prior to conception would be beneficial for them and their child, but cited barriers such as time, location, and the way providers encourage weight loss. Providers were willing to refer to a number of behavioral interventions, and were less willing to prescribe weight loss medications than other intervention options. CONCLUSIONS: A number of intervention strategies may be well received by both patients and providers in preconception care to assist with weight loss prior to conception. Future research is needed on intervention effects and sustainability.

Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis.

The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance.

Endometrial receptivity and intrauterine adhesive disease.

Intrauterine adhesions (IUA) can occur after mechanical or infectious injury to the endometrium. Normal endometrial repair occurs without scar formation; however, in some women, these normal repair mechanisms are aberrant, resulting in IUA formation. The exact alteration in repair mechanisms is not well understood; however, it likely involves hypoxia, reduced neovascularization, and altered expression of adhesion-associated cytokines. The prevalence of IUA varies by the type of injury and ranges from 16 to 24% in women undergoing pregnancy-related curettage and 31 to 45% after hysteroscopic myomectomy. The presence of IUA may result in infertility and/or pregnancy complications; thus, hysteroscopic adhesiolysis is typically recommended before conception. Sharp dissection rather than cautery to resect adhesions and postoperative treatment with an IUA barrier and estrogen may decrease the likelihood of recurrence. Menstrual history before hysteroscopic repair and endometrial thickness after surgical repair may be useful in assessing endometrial receptivity and the likelihood of conception.

Healthcare provider accuracy at estimating women's BMI and intent to provide counseling based on appearance alone.

OBJECTIVE: To assess healthcare providers' ability to estimate women's body mass index (BMI) based on physical appearance and determine the prevalence of, and barriers to, weight-related counseling. METHODS: A web-based survey was distributed to healthcare providers ("participants") at a university-based hospital and contained photographs of anonymous women ("photographed women (PW)") as well as questions regarding participant demographics. Participants were asked to estimate BMI category based on physical appearance, state whether they would provide weight-loss counseling for each PW and identify barriers to counseling. RESULTS: One hundred forty-two participants completed the survey. BMI estimations were poor among all participants, with an overall accuracy of only 41% and a large proportion of underestimations. Standardization of PW clothing did not improve accuracy; 41% for own clothing versus 40% for scrubs, P = 0.2. BMI assessments were more accurate for Caucasian versus African American PW (45% versus 36%, P < 0.001) and PW with normal weight (84%) and obesity III (38%) compared to PW with mid-range BMI (P < 0.001). Although the frequency of weight loss counseling was positively associated with PW BMI, participants only intended to counsel 69% of overweight and obese PW. The most commonly cited reason for lack of counseling was time constraints (54%). CONCLUSIONS: Healthcare providers are inaccurate at appearance-based BMI categorization and thus, BMI should be routinely calculated in order to improve identification of those in need of counseling. When appropriately identified, time constraints may prevent practitioners from providing appropriate weight-loss counseling-further complicating the already difficult task of fighting obesity.

Cervical mucus monitoring prevalence and associated fecundability in women trying to conceive.

OBJECTIVE: To assess the use of cervical mucus monitoring (CMM) in women trying to conceive and determine whether monitoring is associated with increased cycle-specific probability of conception (fecundability). DESIGN: Time-to-pregnancy cohort study. SETTING: Population-based cohort. PATIENT(S): Three hundred thirty-one women trying to conceive, ages 30 to 44 years, without known infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): CMM prevalence and fecundability. RESULT(S): During the first cycle of the study, CMM was performed consistently (checked on >66% of pertinent cycle days) by 20 women (6%), inconsistently (34% to 66% of days) by 60 women (18%), infrequently (≤33% of days) by 73 women (22%), and not performed by 178 women (54%). Cycles in which CMM was consistently performed were statistically significantly more likely to result in conception after adjusting for age, race, previous pregnancy, body mass index, intercourse frequency, and urinary luteinizing hormone (LH) monitoring. Fecundability also increased with increasing consistency of CMM. CONCLUSION(S): Among women trying to conceive, CMM is uncommon, but our study suggests that CMM-a free, self-directed method to determine the fertile window-is associated with increased fecundability independent of intercourse frequency or use of urinary LH monitoring.