Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies.

BACKGROUND: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability. METHODS: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling. RESULTS: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%). CONCLUSIONS: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education.

Alcohol, cigarette smoking, and ovarian reserve in reproductive-age African-American women.

BACKGROUND: Although alcohol consumption and cigarette smoking are common behaviors in reproductive-age women, little is known about the impact of consumption patterns on ovarian reserve. Even less is known about the effects of smoking and alcohol use in reproductive-age African-American women. OBJECTIVE: The objective of the study was to examine the impact of the patterns of alcohol intake and cigarette smoking on anti-Müllerian hormone levels as a marker of ovarian reserve in African-American women. STUDY DESIGN: This was a cross-sectional analysis from the baseline clinical visit and data collection of the Study of Environment, Lifestyle, and Fibroids performed by the National Institute of Environmental Health Sciences. A total of 1654 volunteers, aged 23-34 years, recruited from the Detroit, Michigan community completed questionnaires on alcohol intake and cigarette smoking and provided serum for anti-Müllerian hormone measurement. Multivariable linear and logistic regressions were used as appropriate to estimate the effect of a range of exposure patterns on anti-Müllerian hormone levels while adjusting for potential confounders including age, body mass index, and hormonal contraception. RESULTS: Most participants were alcohol drinkers (74%). Of those, the majority (74%) engaged in binge drinking at least once in the last year. Women who reported binge drinking twice weekly or more had 26% lower anti-Müllerian hormone levels compared with current drinkers who never binged (95% confidence interval, -44, -2, P < .04). Other alcohol consumption patterns (both past and current) were unrelated to anti-Müllerian hormone. The minority of participants currently (19%) or formerly (7%) smoked, and only 4% of current smokers used a pack a day or more. Neither smoking status nor second-hand smoke exposure in utero, childhood, or adulthood was associated with anti-Müllerian hormone levels. CONCLUSION: Results suggest that current, frequent binge drinking may have an adverse impact on ovarian reserve. Other drinking and smoking exposures were not associated with anti-Müllerian hormone in this cohort of healthy, young, African-American women. A longitudinal study of how these common lifestyle behaviors have an impact on the variability in age-adjusted anti-Müllerian hormone levels is merited.

Idiopathic granulomatous mastitis--a prospective study of 49 women and treatment outcomes with steroid therapy.

Idiopathic granulomatous mastitis (IGM) is an infrequently reported benign breast disease of unknown etiology. Surgical treatment has been widely advocated but can be disfiguring. We describe demographic and clinico-pathologic features of women with IGM in a safety net hospital, and evaluate steroid therapy as a breast-conserving modality of treatment. We also examine a possible ethnic predominance in Hispanic women. We conducted an observational prospective cohort study of all women with biopsy-proven granulomatous mastitis in the breast clinics of an urban safety net public hospital from 2006 to 2010. Demographic, ethnic and clinical data, treatment history, and response to treatment were collected. Patients were followed up prospectively to determine the type of treatment prescribed, complete resolution of disease, and median time to resolution. A nested case-control study was conducted to examine Hispanic prevalence using chi-square statistic. The mean age was 35 years. 80% were Hispanic. 80% presented with a painful breast mass. 59% initially received antibiotics with incomplete resolution. 90% women were prescribed oral steroids, 3% underwent surgical treatment, and 6% remained under observation with spontaneous resolution. Of those who received steroid, 80% had complete resolution of disease with a median time to complete resolution of 159 days (IQR 120-241 days). Ethnicity data in a nested case-control study revealed that women in the IGM group were more likely to be Hispanic than in the control group with an odds ratio of 3 (95% CI 1.42-6.24, p-value 0.0032). IGM is a benign but locally aggressive breast disease. Treatment with steroids is an effective breast-conserving option. Predominance in Hispanic women of childbearing age suggests a common genetic, environmental, immunologic, or infectious etiology and warrants further study with a multi-disciplinary approach.

Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.

CONTEXT: Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene. OBJECTIVE: To examine cellular and molecular differences in the endometrium of women with suboptimal vs optimal endometrial thickening following clomiphene. METHODS: Translational prospective cohort study from 2018 to 2020 at a university-affiliated clinic. Reproductive age women with unexplained infertility treated with 100 mg of clomiphene on cycle days 3 to 7 who developed optimal (≥8mm; n = 6, controls) or suboptimal (<6mm; n = 7, subjects) endometrial thickness underwent preovulatory blood and endometrial sampling. The main outcome measures were endometrial tissue architecture, abundance and location of specific proteins, RNA expression, and estrogen receptor (ER) α binding. RESULTS: The endometrium of suboptimal subjects compared with optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%, P = .01), decreased immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), increased immunostaining of pan-leukocyte marker CD45 and ERß, but decreased ERα immunostaining (all P < .05). RNA-seq identified 398 differentially expressed genes between groups. Pathway analysis of differentially expressed genes indicated reduced proliferation (Z-score = -2.2, P < .01), decreased angiogenesis (Z-score = -2.87, P < .001), increased inflammation (Z-score = +2.2, P < .01), and ERß activation (Z-score = +1.6, P < .001) in suboptimal subjects. ChIP-seq identified 6 genes bound by ERα that were differentially expressed between groups (P < .01), some of which may play a role in implantation. CONCLUSION: Women with suboptimal endometrial thickness after clomiphene exhibit aberrant ER expression patterns, architectural changes, and altered gene and protein expression suggesting reduced proliferation and angiogenesis in the setting of increased inflammation.

Does empiric superovulation improve fecundity in healthy women undergoing therapeutic donor insemination without a male partner?

OBJECTIVE: To evaluate whether superovulation improves fecundity in women undergoing therapeutic donor insemination (TDI). DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility clinic. PATIENT(S): Healthy women aged 23-45 years with no history of or risk factors for infertility who underwent 152 medicated and 104 unmedicated TDI cycles from 2013 to 2018. INTERVENTION: Unmedicated TDI versus use of medication in a TDI cycle (clomiphene citrate or letrozole). MAIN OUTCOME MEASURE(S): Cumulative probability of pregnancy in six TDI cycles. RESULT(S): In adjusted all-cycle analysis, medicated TDI cycles were less likely to result in pregnancy compared with unmedicated cycles. The incidence of twins was 23% in the medicated group and 0% in the unmedicated group. Medicated cycles were less likely to result in pregnancy in women younger than 40 years or with an antimüllerian hormone (AMH) level >1.2. After three cycles not resulting in pregnancy, the only women who conceived were those who crossed over from an unmedicated to a medicated cycle (12% vs. 0%). CONCLUSION(S): Patients undergoing unmedicated TDI cycles had higher fecundity and no incidence of twin gestations. Older women, those with low AMH, and those who fail to conceive after three unmedicated cycles may benefit from medication.

Endoscopic Repair of Proximal Hamstring Tear With Double-Row Suture Bridge Construct.

Hamstring strains account for 25% to 30% of all muscle strains and are an exceedingly common injury in the athletic population. Although proximal hamstring avulsion injuries occur less commonly than strains at the myotendinous junction, they are more severe and debilitating. Proximal hamstring avulsions do not respond well to conservative treatment and are more likely to require surgical intervention. Surgical repair of proximal hamstring avulsions is indicated when the injury fails to respond to conservative treatment, in cases of osseous avulsion with retraction, and in cases of tearing of all 3 hamstring tendons. Endoscopic repair of proximal hamstring avulsions is a promising technique to repair these injuries while reducing morbidity. We describe our technique for endoscopic proximal hamstring repair, which uses a double-row suture bridge construct to reattach the tendons to the ischial tuberosity.

Anti-Müllerian hormone as a predictor of reproductive potential.

PURPOSE OF REVIEW: Anti-Müllerian hormone (AMH), a marker of ovarian reserve, declines over a woman's reproductive lifespan. AMH is highly correlated with a woman's age and number of primordial ovarian follicles, and has been shown to predict time to menopause in women in their 40s. For these reasons, it was assumed that AMH levels could predict a woman's reproductive potential or serve as a 'fertility test'. Recently, studies have sought to determine the association between AMH and fertility. RECENT FINDINGS: Although a small, prospective, time-to-pregnancy study of 98 women suggested that an AMH level less than 0.7 ng/ml was associated with lower day-specific probabilities of conception, the follow-up, larger cohort did not identify an association with AMH and fecundability. Women with AMH values less than 0.7 ng/ml had similar pregnancy rates after 12 cycles of attempting to conceive as women with normal AMH values after adjusting for age. Four additional studies, including a secondary analysis of the NICHD EAGER trial including over 1200 women confirmed these findings. SUMMARY: Although AMH is a marker of ovarian reserve, existing literature does not support the use of AMH as a marker of reproductive potential in the general population.

Treatment of endometriosis-related chronic pelvic pain with Ulipristal Acetate and associated endometrial changes.

BACKGROUND: Aberrant progesterone signaling has been demonstrated in mechanistic studies to be a shared common pathway in fibroids and endometriosis. Progesterone receptor modulation with the selective progesterone receptor modulator (SPRM) ulipristal may decrease pain associated with endometriosis. CASE: A 25-year-old nulligravidae with endometriosis-related pelvic pain refractory to medical and surgical intervention was administered 15mg ulipristal every other day for 3 months. Daily pain scores and bleeding diary were recorded and serum chemistries and hormone levels were checked prior to, during, and after treatment. Pre-treatment and surveillance endometrial biopsy specimens were examined for histology and stained for estrogen and progesterone receptor status. During therapy, pain scores decreased to a median of 0 (P<0.05) and the patient became amenorrheic. Surveillance endometrial biopsy demonstrated SPRM-associated endometrial changes that appeared strikingly similar to simple hyperplasia and resolved with ulipristal discontinuation. Immunohistochemical evaluation demonstrated the presence of estrogen and progesterone receptors before and during ulipristal treatment. CONCLUSIONS: Progesterone receptor modulation with ulipristal substantially improved pain symptoms in a patient with treatment-refractory endometriosis. SPRM-associated changes in the endometrium closely mimicked hyperplasia, developed after less than three months of treatment, and resolved after discontinuation of ulipristal and induction of withdrawal bleed.

Lifestyle and in vitro fertilization: what do patients believe?

BACKGROUND: Patients have many beliefs regarding lifestyle factors and IVF outcomes. METHODS: Observational study of 208 IVF patients at an academic infertility center. Main outcome measures were perceived influence of various lifestyle factors assessed by multivariable logistic regression and p-value tests for linear trend (Pt). RESULTS: A majority of participants believed that there were many women's lifestyle choices that were influential, compared to fewer male factors (cessation of tobacco (72 %), alcohol (69 %), caffeine (62 %), and use of vitamins (88 %)). Compared to participants with less education, participants with a higher education level were less likely to believe vitamins were helpful and some alcohol use was not harmful. As income decreased, participants were less likely to consider dietary factors contributory to IVF success, such as women (p-trend, p = 0.02) and men (p-trend, p = 0.009) consuming a full-fat dairy diet. Participants' beliefs were most commonly influenced by physicians (84 %) and the internet (71 %). CONCLUSIONS: Patients believed many lifestyle factors are associated with IVF success. Understanding patients' assumptions regarding the effect of lifestyle factors on IVF success may better allow physicians to counsel patients about IVF outcomes.

Perineal Post Padding Technique to Improve Hip Distraction in Tall Patients.

Hip distraction is necessary for safe arthroscopic entry into the hip joint. Achieving sufficient distraction is difficult in exceedingly tall patients (>190.5 cm) because of size limitations of currently available hip distraction systems. Inadequate distraction can delay the surgical procedure and potentially lead to complications. By repurposing a foam head-positioning block, we report a safe and inexpensive positioning technique for extending the traction distance for tall patients by 2 inches.

Factors associated with second-trimester pregnancy loss in women with normal uterine anatomy undergoing in vitro fertilization.

OBJECTIVE: To evaluate factors associated with second-trimester pregnancy loss in patients with normal uterine anatomy who conceived through in vitro fertilization. METHODS: Women aged 21-44 years with ongoing in vitro fertilization pregnancy (at least one fetus with fetal heart tones at 12 weeks of gestation) at an academic hospital from 2001 to 2012 were eligible for inclusion in this retrospective cohort. Comprehensive uterine evaluation permitted inclusion of only women with anatomically normal uterine cavities. Maternal and clinical characteristics associated with spontaneous second-trimester pregnancy loss (between 12 1/7 and 23 6/7 weeks of gestation) were assessed. Multivariable logistic regression generated adjusted odds ratios (ORs), 95% confidence intervals (CIs), and Wald two-sided P values. RESULTS: Among ongoing second-trimester pregnancies, 60 (2.1%) ended in spontaneous pregnancy loss and 2,841 (97.9%) ended in live birth. Multiple gestations (twins or more) conferred greater odds of pregnancy loss (adjusted OR 1.93, CI 1.15-3.24, P=.01) and were more prevalent among losses (48.3%) than live births (34.1%). Uterine leiomyomas were present in 16.7% of losses and 4.7% of live births and were associated with a nearly fourfold increased odds of second-trimester pregnancy loss (adjusted OR 3.82, CI 1.85-7.89, P<.001). Women with obese body mass index ([BMI] 30 or higher) at cycle start experienced twofold greater odds of pregnancy loss compared with normal-weight women (adjusted OR 2.38, CI 1.05-5.65, P=.04). There were eight obese women (32%) among losses and 209 obese women (16.5%) among live births. In vitro fertilization treatment parameters were not associated with odds of second-trimester loss nor were maternal age, ethnicity, or history of recurrent pregnancy loss. CONCLUSION: Odds of second-trimester spontaneous pregnancy loss among in vitro fertilization conceived pregnancies were greater with multiple gestations, leiomyomas, and obese maternal BMI. LEVEL OF EVIDENCE: II.