Association between diminished ovarian reserve and luteal phase deficiency.

OBJECTIVE: To determine the association between biomarkers of ovarian reserve and luteal phase deficiency (LPD). DESIGN: Secondary analysis of a prospective time-to-conceive cohort study. SETTING: Not applicable. PATIENT(S): Women attempting conception, aged 30-44 years, without known infertility. INTERVENTION(S): Measurement of early follicular phase serum levels of antimüllerian hormone, FSH, inhibin B, and E2. MAIN OUTCOME MEASURE(S): The primary outcome was LPD, defined by luteal bleeding (LB) (≥1 day of LB) or a short luteal phase length (≤11 days). RESULT(S): Overall, 755 women provided information on 2,171 menstrual cycles and serum for measurement of at least one biomarker of ovarian reserve. There were 2,096 cycles from 754 women in the LB cohort, of which 40% experienced LB. After adjusting for age, race, previous miscarriages, and previous pregnancies, diminished ovarian reserve (DOR) was not significantly associated with LB. Low early follicular phase FSH levels increased the odds of LB (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.25-2.71), as did high early follicular phase E2 levels (OR 1.59; 95% CI 1.26-2.01). A total of 608 cycles from 286 women were included in the analysis of luteal phase length, of which 13% had a short luteal phase. After adjusting for age, there was no significant association between DOR and a short luteal phase. The risk of a short luteal phase decreased with increasing inhibin B (OR 0.61; 95% CI 0.45-0.81). CONCLUSION(S): Although DOR is not associated with LPD, hormone dysfunction in the early follicular phase may contribute to LPD in women of older reproductive age.

Screening for Psychological Conditions in Infertile Women: Provider Perspectives.

PURPOSE: To determine if reproductive specialists are screening new patients for depression or anxiety, explore possible reasons why providers are not screening, and assess physician's views about the impact of mental health disorders on fertility. MATERIALS AND METHODS: Cross-sectional exploratory study in which 86 practicing reproductive physicians filled out a 20-question survey regarding mental health screening and perception of psychological disorders on reproduction. RESULTS: The majority of infertility providers believe psychological conditions negatively impact pregnancy success (75%); however, most providers are not formally screening patients for depression or anxiety (28%). Providers who did not screen for depression were more likely to be uncomfortable assessing patients for mental health disorders and to work in a private practice setting. CONCLUSIONS: This study finds that most infertility specialist respondents believe that mental health conditions negatively impact reproductive outcomes; however, few of these providers are screening for psychological disorders in infertile women. Reasons why providers are not screening infertility patients for psychological disorders include lack of time and unfamiliarity with recommendations for treatment of mental health conditions. Implementing a rapid screen for anxiety and depression and providing easily assessable succinct educational updates to fertility providers on current treatment options for mental health disorders may allow affected patients to be treated sooner, and ultimately, may improve fertility outcomes.

Effects of perfluorinated chemicals on thyroid function, markers of ovarian reserve, and natural fertility.

Perfluorinated chemicals (PFCs) can act as endocrine-disrupting chemicals, but there has been limited study of their effects on ovarian reserve or fecundability. 99 women, 30-44 years old, without infertility were followed until pregnancy. Initially, serum was evaluated for Antimullerian hormone (AMH), thyroid hormones: thyroid stimulating hormone (TSH), thyroxine (T4), free thyroxine (fT4), and triiodothyronine (T3), and PFCs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS). Bivariate analyses assessed the relationship between thyroid hormones, AMH, and PFCs. Fecundability ratios (FR) were determined for each PFC using a discrete time-varying Cox model and a day-specific probability model. PFC levels were positively correlated with each other (r 0.24-0.90), but there was no correlation with TSH (r 0.02-0.15) or AMH (r -0.01 to -0.15). FR point estimates for each PFC were neither strong nor statistically significant. Although increased exposure to PFCs correlates with thyroid hormone levels, there is no significant association with fecundability or ovarian reserve.

Infertile women who screen positive for depression are less likely to initiate fertility treatments.

STUDY QUESTION: Are infertile women who screen positive for depression less likely to initiate infertility treatments? SUMMARY ANSWER: Infertile women who screen positive for depression are less likely to initiate treatment for infertility. WHAT IS ALREADY KNOWN: Infertility imposes a psychological burden on many couples. Depression and anxiety have been demonstrated in ~40% of infertile women, which is twice that of fertile women. Further, the psychological burden associated with infertility treatment has been cited as a major factor for discontinuation of infertility care. STUDY DESIGN, SIZE, DURATION: Prospective, observational study in a clinical-based cohort of 416 women who completed a questionnaire after the new patient visit, from January 2013 until December 2014 inclusive. PARTICIPANTS/MATERIALS, SETTING, METHODS: All new female infertility patients (n = 959) seen between January 2013 and December 2014 at University of North Carolina Fertility received an electronic questionnaire to screen for mental health disorders and to evaluate their perception of mental health disorders on infertility. MAIN RESULTS AND THE ROLE OF CHANCE: Of 959 surveys sent, 416 women completed the questionnaire (43%). The prevalence screening positive for depression, using the NIH PROMIS screening tool, was 41%. Sixty-two percent of all women initiated infertility treatment, and of these, 81% did so within 4 months. In multivariate analysis, women who screened positive for depression had 0.55 times the odds of initiating treatment for infertility (95% CI: 0.31-0.95). Similarly, women who screened positive for depression had 0.58 times the odds of initiating infertility treatment within 4 months (95% CI: 0.35-0.97), which was the time of censoring from the most recent patient evaluated. Women who screened positive for depression were less likely to pursue treatment with oral medications or IVF (P = 0.01 and P = 0.03, respectively), as compared to women who did not screen positive for depression. LIMITATIONS, REASONS FOR CAUTION: Questionnaire-based evaluations may result in a lower prevalence of psychological disorder as some participants feign emotional well-being. Although we did not identify differences in women who responded to our survey and those who did not, responder bias may still be present. In addition, infertility is a couple's disease. However, this study only included psychological evaluation of the female partner. We have no information about the women's previous treatment. WIDER IMPLICATIONS OF THE FINDINGS: Screening for depression is important in the infertility patient population, as further evaluation and psychological interventions may improve compliance with fertility treatments, quality of life, and potentially, the overall chance of pregnancy. STUDY FUNDING/COMPETING INTERESTS: None.

Prospective evaluation of luteal phase length and natural fertility.

OBJECTIVE: To evaluate the impact of a short luteal phase on fecundity. DESIGN: Prospective time-to-pregnancy cohort study. SETTING: Not applicable. PATIENT(S): Women trying to conceive, ages 30-44 years, without known infertility. INTERVENTION(S): Daily diaries, ovulation prediction testing, standardized pregnancy testing. MAIN OUTCOME MEASURE(S): Subsequent cycle fecundity. RESULT(S): Included in the analysis were 1,635 cycles from 284 women. A short luteal phase (≤11 days including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy in the subsequent cycle immediately following the short luteal phase compared with women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months there was no significant difference in cumulative probability of pregnancy. CONCLUSION(S): Although an isolated cycle with a short luteal phase may negatively affect short-term fertility, incidence of infertility at 12 months was not significantly higher among these women. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365.

Thyroid Autoimmunity and Reproductive Function.

Thyroid hormones are important for normal reproductive function, and maternal thyroid dysfunction has been associated with infertility, miscarriage, preterm birth, and poor neurodevelopment in the offspring. Thyroid autoimmunity is the leading cause of thyroid dysfunction in women of reproductive age. Women with thyroid autoimmunity, even with normal thyroid function, appear to be at a higher risk for poor reproductive outcomes, including miscarriage and preterm birth. Thyroxine replacement in women with thyroid autoimmunity with or without appreciable thyroid dysfunction may improve pregnancy outcomes. Thus, identification and treatment of women with thyroid autoimmunity may optimize reproductive success.

Prospective evaluation of the impact of intermenstrual bleeding on natural fertility.

OBJECTIVE: To evaluate the impact of an episode of intermenstrual bleeding on the probability of conception in a menstrual cycle (fecundability). DESIGN: Prospective, time-to-pregnancy cohort study. SETTING: Community-based cohort. PATIENT(S): Women trying to conceive, ages 30 to 44 years, without known infertility. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Current cycle and subsequent cycle fecundability. RESULT(S): A total of 549 women provided 1,552 complete cycles for analysis. Intermenstrual and luteal bleeding were reported in 36% and 34% of cycles, respectively. Ninety-three percent of all intermenstrual bleeding was luteal. Cycles in which women had intermenstrual bleeding or luteal bleeding were statistically significantly less likely to result in conception (fecundability ratio [FR] 0.23; 95% confidence interval [CI], 0.16-0.34; and FR 0.22; 95% CI, 0.14-0.33). Women with an episode of intermenstrual and luteal bleeding had a statistically significant increase in the probability of pregnancy in the subsequent cycle (FR 1.61; 95% CI, 1.15-2.25; and FR 2.01; 95% CI, 1.52-2.87, respectively). CONCLUSION(S): Intermenstrual bleeding statistically significantly decreases the odds of conceiving in that cycle but does not appear to negatively impact a woman's immediate future reproductive potential. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365.

Bleeding after laparoscopic supracervical hysterectomy managed with cervical artery embolization. A case report.

BACKGROUND: Postoperative bleeding is a known complication after laparoscopic supracervical hysterectomy (LASH), and trachelectomy is the traditional management of significant bleeding. CASE: We present the case of a patient with significant postoperative bleeding 1 month after LASH, resulting in symptomatic anemia requiring blood transfusion. Gelfoam embolization of the bilateral cervical arteries was successful in stopping the bleeding. The patient had no further bleeding and had resolution of anemia at 6 months postprocedure. CONCLUSION: Our case demonstrates a successful multidisciplinary and minimally invasive approach to management of postoperative bleeding with bilateral cervical artery embolization and should be considered as a potential treatment option.

Age-related infertility.

Oocyte number and quality decrease with advancing age. Thus, fecundity decreases as age increases, with a more rapid decline after the mid-30s. Patients more than 35 years old should receive prompt evaluation for causes of infertility after no more than 6 months of attempted conception. Patients with abnormal tests of ovarian reserve have a poorer prognosis and may need more expedited and aggressive treatment. Although oocyte donation is the best method to overcome age-related infertility, other treatment options may help women proceed quicker toward pregnancy. Patients at an advanced age should be counseled and evaluated before undergoing infertility treatments.

Pneumomediastinum after robotic sacrocolpopexy.

BACKGROUND: Pneumomediastinum is a rare but potential complication of laparoscopy that is related to insufflation with carbon dioxide gas and may lead to life-threatening complications. CASE: A 76-year-old woman underwent robotic sacrocolpopexy to repair posthysterectomy prolapse without any apparent intraoperative complications. Postoperatively, she developed shortness of breath and tachycardia and was found to have subcutaneous emphysema and pneumomediastinum. CONCLUSION: Pelvic surgeons should understand the risks associated with development of pneumomediastinum as well as associated signs and symptoms. In our case, pneumomediastinum likely developed as carbon dioxide tracked from the peritoneum into the mediastinum during prolonged robotic retroperitoneal surgery. Surgeons should have a low threshold to obtain radiographic tests in the early postoperative period, as close monitoring is essential to manage potentially life-threatening complications such as pneumothorax and cardiac arrest.

GATA augments GNRH-mediated increases in Adcyap1 gene expression in pituitary gonadotrope cells.

Pituitary adenylate cyclase-activating polypeptide 1 (PACAP or ADCYAP1) regulates gonadotropin biosynthesis and secretion, both alone and in conjunction with GNRH. Initially identified as a hypothalamic-releasing factor, ADCYAP1 subsequently has been identified in pituitary gonadotropes, suggesting it may act as an autocrine-paracrine factor in this tissue. GNRH has been shown to increase pituitary Adcyap1 gene expression through the interaction of CREB and jun/fos with CRE/AP1 cis-elements in the proximal promoter. In these studies, we were interested in identifying additional transcription factors and cognate cis-elements which regulate Adcyap1 gene promoter activity and chose to focus on the GATA family of transcription factors known to be critical for both pituitary cell differentiation and gonadotropin subunit expression. By transient transfection and electrophoretic mobility shift assay analysis, we demonstrate that GATA2 and GATA4 stimulate Adcyap1 promoter activity via a GATA cis-element located at position -191 in the rat Adcyap1 gene promoter. Furthermore, we show that addition of GATA2 or GATA4 significantly augments GNRH-mediated stimulation of Adcyap1 gene promoter activity in the gonadotrope LßT2 cell line. Conversely, blunting GATA expression with specific siRNA inhibits the ability of GNRH to stimulate ADCYAP1 mRNA levels in these cells. These data demonstrate a complex interaction between GNRH and GATA on ADCYAP1 expression, providing important new insights into the regulation of gonadotrope function.

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the hypothalamic-pituitary-gonadal axis: a review of the literature.

Pituitary adenylate cyclase-activating polypeptide (PACAP), an ancient molecule highly preserved across species, has been classified as a member of the secretin/glucagon/vasoactive intestinal peptide/growth hormone-releasing hormone polypeptide family. PACAP was first identified as a hypothalamic-releasing factor; nevertheless, it has subsequently been determined to have widespread distribution and function, including expression in the pituitary, gonads, placenta, central and peripheral nervous systems, intestinal tract, and adrenal gland. Consistent with its widespread distribution, PACAP has been found to exert pleiotropic effects. Although first described over 20 years ago, only relatively recently has substantial attention turned to evaluating PACAP's role in the reproductive system. This review will focus on our current understanding of the expression pattern and function of PACAP in the hypothalamic-pituitary-gonadal axis.

Under the influence with a child in the car: implications for child safety and caregiver intervention.

BACKGROUND: Injury is the leading cause of death for those aged 1 year to 44 years in the United States, with motor vehicle collisions (MVCs) the leading cause of injury-related deaths. Little data exist on the relationship between caregiver alcohol and drug use at the time of MVC and child passenger outcomes. We examined the relationship between caregiver substance use in MVCs and a number of demographic, crash severity, and medical outcomes for caregivers and children. METHODS: We identified family groups treated in the emergency department of a regional Level II trauma center after an MVC in a 1-year period from July 1, 2005, to June 30, 2006. The distribution and means of characteristics for substance and nonsubstance users were compared using χ analysis and Student's t tests, respectively. RESULTS: One in 10 vehicles contained an intoxicated caregiver at the time of MVC. In 363 identified caregivers, intoxication was associated with being male (p < 0.001), lack of safety device use (p = 0.003), rollover (p = 0.008), and ejection (p = 0.016). In the 278 family groups, intoxicated caregivers were related to child ejection (p = 0.009), the need for child hospital admission (p < 0.001), and driver intoxication was related to child lack of restraint (p = 0.045). CONCLUSION: These findings suggest a substantial number of child MVC victims arrive at the emergency room after riding with an intoxicated caregiver. Findings support the need for prevention programs focusing on substance use and driving for male caregivers, and further investigation on the need for screening and intervention for caregivers' risky alcohol and drug use after a child's MVC.

Efficacy of an accelerated hepatitis B vaccination program during pregnancy.

OBJECTIVE: To estimate the feasibility and immunogenicity of an accelerated hepatitis B vaccination schedule of 0, 1, and 4 months in high-risk pregnant women. METHODS: We conducted a prospective clinical trial of high-risk pregnant women who were hepatitis B surface antigen-negative at presentation for prenatal care. A detailed questionnaire was administered and eligible women received a hepatitis B vaccine intramuscularly on a 0-, 1-, and 4-month schedule. Adverse reactions and hepatitis B surface antigen seroconversion rates were documented. Factors influencing seroconversion were determined. RESULTS: Two hundred high-risk pregnant women were enrolled; 84% completed the three-dose vaccine series. Seroconversion (hepatitis B surface antigen 10 milli-international units/mL or greater) after one dose was 56% (95% confidence interval [CI], 49-63%), 77% (95% CI, 71-83%) after two doses, and 90% (95% CI, 85-94%) after completing three doses. Body mass index was inversely associated with seroconversion rates (P<.001). There was no single body mass index above which seroconversion did not occur. There were no serious adverse events; injection site discomfort was the most prevalent complaint (10.5%). CONCLUSION: An accelerated hepatitis B vaccination schedule at 0, 1, and 4 months in high-risk pregnant women is effective, practical, and well tolerated. This accelerated vaccine strategy can be completed during the course of pregnancy and provides another means of decreasing hepatitis B virus disease and transmission.