Considerations for management of interstitial ectopic pregnancies: two case reports.

BACKGROUND: Conventional treatment of interstitial pregnancies includes systemic methotrexate, direct methotrexate injection, wedge resection, or hysterectomy. We present two cases of interstitial pregnancies that were successfully managed by different minimally invasive surgical techniques. We also report the novel use of hysteroscopic urologic stone retrieval forceps in the transvaginal removal of persistent products of conception after systemic methotrexate for an interstitial pregnancy. CASE PRESENTATION: Case 1 was a 28-year-old gravida 1 white woman at 8 weeks gestation; she was diagnosed with a left interstitial pregnancy. After laparoscopic confirmation of the interstitial pregnancy, successful ultrasound-guided suction dilation and curettage was performed. Case 2 was a 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with persistent products of conception after systemic methotrexate for a left interstitial pregnancy. She underwent hysteroscopic-guided removal of the persistent products of conception, which was possible due to novel use of urologic stone retrieval forceps. CONCLUSIONS: Successful minimally invasive treatment of interstitial pregnancies may be possible in certain cases. Collaboration between different specialties continues to be important for improving minimally invasive options.

Menopause and exercise.

OBJECTIVE: Accumulating data suggest that regular physical exercise reduces mortality and extends the functional life span of men and women. This review seeks to describe the current state of the medical literature on this topic. METHODS: A narrative review of the current medical literature including randomized clinical trials and clinical guidelines that address the benefits of physical fitness and regular exercise on the health of midlife and postmenopausal women. RESULTS: Reduction and avoidance of obesity and its related comorbidities (hypertension, glucose intolerance, dyslipidemia, and heart disease) are one major benefit of exercise. However, long-term physical exercise is also associated with reduced rates of cancer, dementia and cognitive decline, adverse mood and anxiety symptoms, and reduction of osteoporosis, osteopenia, falls, and fractures. Beneficial physical activity includes exercise that will promote cardiovascular fitness (aerobic), muscle strength (resistance), flexibility (stretching), and balance (many of the preceding, and additional activities such as yoga). CONCLUSIONS: Given that it is unambiguously beneficial, inexpensive, and minimal risk, maintaining a healthy exercise regimen should be a goal for every participant to enhance lifelong wellness. Clinicians should use a number of behavioral strategies to support the physical fitness goals of their participants.

Variability in the practice of fertility preservation for patients with cancer.

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

Antral follicle count is increased in obese women placed on oral contraceptive pills.

OBJECTIVE: To determine the effect of short-term combined oral contraceptive (OCP) use on antral follicle count (AFC) in obese and nonobese women with infertility. STUDY DESIGN: A retrospective review of women who had an AFC (sum of 2-10 mm bilateral ovarian follicles on basal follicular phase ultrasound) measured before and after short-term OCP use between the years 2005 and 2010. These were women who had a baseline AFC measurement during an unsuccessful controlled ovarian hyperstimulation/intrauterine insemination who were then placed on OCPs prior to an in vitro fertilization (IVF) cycle that included a subsequent AFC measurement at baseline. RESULTS: A total of 57 IVF cycles met criteria for inclusion in the study. AFC was not impacted by OCP use in the nonobese cohort (BMI < 30). Baseline AFC in obese women (BMI ≥ 30), however, increased after OCP use (18 ± 6 vs. 28 ± 9, p = 0.002). CONCLUSION: Use of suppressive medications like OCPs in obese women increases AFC during IVF, potentially by AFC cohort synchrony. This observation warrants consideration when using AFC to predict gonadotropin/ART response as well as future prospective research to further elucidate potential etiologies.

Persistent organic pollutants and early menopause in U.S. women.

OBJECTIVE: Endocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause. METHODS: Cross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years. FINDINGS: This analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of ß-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women. CONCLUSIONS: This study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

State-mandated insurance coverage is associated with the approach to hydrosalpinges before IVF.

The aim of this study was to determine whether practice in states with infertility insurance mandates is associated with physician-reported practice patterns regarding hydrosalpinx management in assisted reproduction clinics. A cross-sectional, internet-based survey of 442 members of Society for Reproductive Endocrinology and Infertility or Society of Reproductive Surgeons was performed. Physicians practising in states without infertility insurance mandates were more likely to report performing diagnostic surgery after an inconclusive hysterosalpingogram than physicians practising in states with mandates (RR 1.2, 95% CI 1.1-1.3, P < 0.01). Additionally, respondents in states without mandates were more likely to report that, due to lack of infertility insurance coverage, they did not perform salpingectomy (SPX) or proximal tubal occlusion (PTO) before assisted reproduction treatment (RR 1.4, 95% CI 1.1-1.8, P = 0.01). Finally, respondents in states without mandates were less likely to report that the presence of assisted reproduction treatment coverage determined the urgency with which they pursued SPX or PTO before treatment (RR 0.7, 95% CI 0.5-1.0, NS). These results persisted after controlling for physician years in practice, age and clinic volume. In conclusion, self-reported physician practice interventions for hydrosalpinges before assisted reproduction treatment may be associated with state-mandated infertility insurance. Fallopian tube dysfunction is a known cause of infertility and severe dysfunction is manifested by dilation and occlusion, known as hydrosalpinx. Outcomes with assisted reproductive techniques (ART) are lower when hydrosalpinges are present and while there are several theories for this, reproductive specialist recommend "neutralizing" the tube either by occlusion or removal in order to enhance pregnancy rates. In the United States, coverage for infertility services is not uniform with only 15 states having some legislation requiring infertility benefits. Some states where ART is covered liberally, physicians might have different practice patterns related to the neutralization of hydrosalpinges compared to those who are in non -mandated states. We utilized a survey of over 400 providers in the United States to examine their practice patterns as it relates to hydrosalpinges based on which state they practice in and whether or not that state has mandated coverage of not.

DHEA-mediated inhibition of the pentose phosphate pathway alters oocyte lipid metabolism in mice.

Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often elevated in women with PCOS. Treated mice had polycystic ovaries, low ovulation rates, disrupted estrous cycles, and altered hormone levels. Because DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose-6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from these mice were significantly lower than controls, suggesting abnormal tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and citrate effects were reversible by supplementation with nicotinic acid, a precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings suggest that elevations in systemic DHEA can have a negative impact on oocyte metabolism and may contribute to poor pregnancy outcomes in women with hyperandrogenism and PCOS.

Maternal obesity, infertility and mitochondrial dysfunction: potential mechanisms emerging from mouse model systems.

Obesity is associated with ovulatory disorders, decreased rates of conception, infertility, early pregnancy loss and congenital abnormalities. Poor oocyte quality and reduced IVF success have also been reported in obese women. Recent attempts to understand the mechanism by which these defects occur have focused on mitochondria, essential organelles that are critical for oocyte maturation and subsequent embryo development. The oocyte relies on maternally supplied mitochondria until the resumption of mitochondrial replication in the peri-implantation period. Here we review current literature addressing the roles of mitochondria in oocyte function and how mitochondrial dysfunction can lead to fertility problems. The relationship between mitochondrial dysfunction and oocyte function is evaluated by examining the following examples of environmental exposures: tobacco smoke, aging, caloric restriction and hyperglycemia. Finally, we present new data from a mouse model of obesity that has demonstrated that oocyte mitochondria play a key role in obesity-associated reproductive disorders.

High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects.

BACKGROUND: Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. METHODOLOGY/PRINCIPAL FINDINGS: We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. CONCLUSIONS/SIGNIFICANCE: Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes.

How members of the Society for Reproductive Endocrinology and Infertility and Society of Reproductive Surgeons evaluate, define, and manage hydrosalpinges.

OBJECTIVE: To describe the management of hydrosalpinges among Society for Reproduction Endocrinology and Infertility (SREI)/Society of Reproductive Surgeons (SRS) members. DESIGN: Cross-sectional survey of SREI/SRS members. SETTING: Academic and private practice-based reproductive medicine physicians. PARTICIPANT(S): A total of 442 SREI and/or SRS members. INTERVENTION(S): Internet-based survey. MAIN OUTCOME MEASURE(S): To understand how respondents evaluate, define, and manage hydrosalpinges. RESULT(S): Of 1,070 SREI and SRS members surveyed, 442 responded to all items, for a 41% response rate. Respondents represented both academic and private practice settings, and differences existed in the evaluation and management of hydrosalpinges. More than one-half (57%) perform their own hysterosalpingograms (HSGs), and 54.5% involve radiologists in their interpretation of tubal disease. Most respondents thought that a clinically significant hydrosalpinx on HSG is one that is distally occluded (80.4%) or visible on ultrasound (60%). Approximately one in four respondents remove a unilateral hydrosalpinx before controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI) and clomiphene citrate (CC)/IUI (29.3% and 22.8%, respectively), and physicians in private practice were more likely to intervene (COH: risk ratio [RR] 1.81, 95% confidence interval [CI] 1.31-2.51; CC: RR 1.98, 95% CI 1.33-2.95). Although laparoscopic salpingectomy was the preferred method of surgical management, nearly one-half responded that hysteroscopic tubal occlusion should have a role as a primary method of intervention. CONCLUSION(S): SREI/SRS members define a "clinically significant hydrosalpinx" consistently, and actual practice among members reflects American Society for Reproductive Medicine/SRS recommendations, with variation attributed to individual patient needs. Additionally, one in four members intervene before other infertility treatments when there is a unilateral hydrosalpinx present.