Divya K. Shah

Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization.

OBJECTIVE: To estimate the effect of body mass index (BMI) on oocyte and embryo parameters and cycle outcomes in women undergoing in vitro fertilization (IVF). METHODS: We evaluated a retrospective cohort of 1,721 women undergoing a first IVF cycle with fresh, autologous embryos between 2007 and 2010 in an academic infertility practice. Main outcome measures included number of mature and normally fertilized oocytes, embryo morphology, estradiol on the day of human chorionic gonadotropin administration, clinical pregnancy, spontaneous abortion, and live birth. We performed multivariable analyses, adjusting for potential confounders, including age at cycle start, infertility diagnosis, type of stimulation, total gonadotropin dose, use of intracytoplasmic sperm injection, and number of embryos transferred. RESULTS: Compared with women of normal BMI, women with class II (BMI 35–39.9) and III (BMI 40 or higher) obesity had fewer normally fertilized oocytes (9.3 compared with 7.6 and 7.7, P<.03) and lower estradiol levels (2,047 pg/mL compared with 1,498 and 1,361, P<.001) adjusting for age and despite similar numbers of mature oocytes. Odds of clinical pregnancy (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.31–0.82) and live birth (OR 0.51, 95% CI 0.29–0.87) were 50% lower in women with class III obesity as compared with women of normal BMI. CONCLUSION: Obesity was associated with fewer normally fertilized oocytes, lower estradiol levels, and lower pregnancy and live birth rates. Infertile women requiring IVF should be encouraged to maintain a normal weight during treatment. LEVEL OF EVIDENCE: II

Bariatric surgery and fertility

Purpose of review Bariatric surgery is the most reliable way to sustain weight loss in the morbidly obese. Reproductive age women comprise the majority of bariatric patients, and many may be interested in conceiving after surgery. The purpose of this review is to synthesize the recent literature on bariatric surgery and fertility to assist providers in patient counseling. Recent findings Obesity adversely impacts fecundability and IVF outcomes through a variety of mechanisms. The body of literature on reproductive outcome after bariatric surgery is sparse and of mixed quality. Bariatric surgery has been shown to improve menstrual cyclicity in anovulatory women, but little is published on the impact of surgical weight loss on spontaneous or IVF-treatment-related pregnancy rates. The increased risk of miscarriage in obese women may decline after bariatric surgery. There are currently insufficient data to support recommendations regarding the ideal timing for pregnancy after bariatric surgery. Summary Obesity has been shown to adversely impact fertility, and weight loss is associated with significant improvement in many parameters of reproductive function. Further research is required as to the specific impact of surgical weight loss on pregnancy and miscarriage rates, as well as the optimal timing of pregnancy after bariatric surgery.

Pharmacokinetics of Human Chorionic Gonadotropin Injection in Obese and Normal-Weight Women

CONTEXT Obese women have poorer in vitro fertilization outcomes, but underlying mechanisms remain unclear. OBJECTIVE The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin (hCG) and ovarian steroid hormone production, after subcutaneous (s.c.) and intramuscular (i.m.) injection of hCG in obese and normal-weight women. DESIGN AND SETTING This was a randomized, experimental study. PATIENTS OR OTHER PARTICIPANTS Twenty-two women aged 18-42 years with body mass index of 18.5-24.9 (normal) or 30-40 kg/m(2) (obese). INTERVENTIONS Participants received im urinary hCG or s.c. recombinant hCG and returned for a second injection type after a 4-week washout. Intramuscular injections were performed under ultrasound guidance. Blood was taken 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 36 hours after injection. MAIN OUTCOME MEASURES hCG was measured at each time point; estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), testosterone (T), dehydroepiandrosterone, and SHBG were measured at 0 and 36 hours. RESULTS Twenty-two women completed the study. In both normal-weight and obese women, peak serum concentration (Cmax), area under the curve (AUC), and average hCG concentration were higher after i.m. injection as compared with s.c. injection (all P < .003). Obese women had markedly lower Cmax, AUC, and average hCG concentration after s.c. injection as compared with normal-weight women (P = .02, P = .009, and P = .008, respectively). After i.m. injection, Cmax, AUC, and average concentration were similar for normal-weight and obese women (P = .31, P = .25, and P = .18, respectively). Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle. hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an increase in T in obese but not normal-weight women (all P < .04). CONCLUSIONS Subcutaneous injection yields lower hCG levels in obese women. Standard-length needles are insufficient to administer i.m. injections in many obese women.

Effect of surgery for endometrioma on ovarian function.

Endometriosis affects a significant proportion of reproductive-aged women. The impact of the disease on ovarian function is an important consideration when planning treatment in women who want to retain the potential of future childbearing. This review will specifically address the association between endometriomas and diminished ovarian reserve, with a particular focus on the impact of surgical endometrioma resection on ovarian function. The existing literature supports an adverse effect of ovarian endometriomas on spontaneous ovulation rates, markers of ovarian reserve, and response to ovarian stimulation, although data on clinical pregnancy and live birth rates remain inconsistent. Surgical removal of endometriomas may worsen ovarian function by removing healthy ovarian cortex or compromising blood flow to the ovary. It is evident that surgical excision of endometriomas acutely impairs ovarian function as measured by ovarian reserve markers; whether this represents progressive or long term impairment remains the subject of ongoing investigation.

Association of body mass index and morbidity after abdominal, vaginal, and laparoscopic hysterectomy.

OBJECTIVE: To examine the association of body mass index (BMI) and operative time and perioperative morbidity after hysterectomy and determine whether the association varies among abdominal, laparoscopic, and vaginal approaches. METHODS: Data abstracted from the American College of Surgeons National Safety and Quality Improvement Project registry included 55,409 women who underwent hysterectomy for benign conditions between January 2005 and December 2012. The relationships among BMI, operative time, and morbidity were examined, adjusting for age, race, ethnicity, year of surgery, smoking, diabetes, and American Society for Anesthesiologists physical classification. Adjusted means, incidence rate ratios, or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using linear, Poisson, or logistic regression, respectively. RESULTS: Body mass index was positively correlated with risk of wound complications and infection in women undergoing abdominal hysterectomy. Compared with those of normal BMI, women with BMIs 40 or higher had five times the odds of wound dehiscence (2.1% compared with 0.3%, crude OR 7.35, CI 3.78–14.30; adjusted OR 5.33, CI 2.63–10.8), five times the odds of wound infection (8.9% compared with 1.4%, crude OR 6.81, CI 5.00–9.27; adjusted OR 5.34, CI 3.85–7.41), and 89% higher odds of sepsis (1.3% compared with 0.6%, crude OR 2.39, CI 1.35–4.24; adjusted OR 1.89, CI 1.01–3.52). The magnitude of the association between wound infection and BMI was smaller after vaginal hysterectomy, and no increased odds of wound complications or sepsis were noted with a laparoscopic approach despite longer operative times. Operative time increased with BMI regardless of surgical approach. No associations were noted between BMI and hospital stay or thromboembolism. CONCLUSION: Obesity is associated with increased wound complications and infection in women undergoing abdominal hysterectomy and with longer operative times regardless of surgical approach. Vaginal or laparoscopic hysterectomy should be performed whenever feasible. LEVEL OF EVIDENCE: II

Medical, ethical, and legal considerations in fertility preservation

The past 2 decades have seen a significant rise in cancer survival rates, and an increasing proportion of survivors at reproductive age are interested in childbearing. Although assisted reproduction provides physicians with an array of potential possibilities to help patients whose fertility is compromised by cancer treatment, there is still a dearth of regulation regarding the application of this technology. The present paper reviews the current options for fertility preservation, with a particular focus on the legal and ethical challenges that confront providers of this type of care.

Population-based study of attitudes toward posthumous reproduction

OBJECTIVE To measure public attitudes toward posthumous reproduction. DESIGN Cross-sectional study. SETTING Electronic survey. PATIENT(S) A total of 1,049 men and women living in the United States between the ages of 18 and 75 years. INTERVENTION(S) Multiple-choice questionnaire. MAIN OUTCOME MEASURE(S) Descriptive statistics regarding support for posthumous reproduction, such as regarding emergency harvesting of gametes, and attitudes toward consent; multivariable analyses of demographic and personal experiences associated with support for posthumous reproduction. RESULT(S) Results showed that 47.8% supported and 31.1% opposed retrieving gametes from men, and 42.7% supported and 35.9% opposed retrieving gametes from women. The remainder was undecided. Among supporters, 69.8% believed prior consent from the deceased was required. Support was positively associated with younger age, higher education, higher income, Democratic political party affiliation, history of infertility, and currently attempting conception. Gender, religion, race, and region of the country were not associated with support. Organ donors and those who support IVF were more likely to support posthumous reproduction (odds ratio [95% confidence interval] 1.68 [1.19-2.38] and 12.30 [6.56-23.04], respectively). Most respondents were initially unfamiliar with posthumous reproduction. CONCLUSION(S) Almost 50% of the general population support posthumous reproduction in men and women. The majority favored prior consent from the deceased. These data caution against emergency gamete harvesting without prior consent.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome with a single uterus

OBJECTIVE To describe an unusual case of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome with a single uterus. DESIGN Case report. SETTING Major academic medical center. PATIENT(S) A 12-year-old girl with OHVIRA syndrome. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) None. RESULT(S) A 12-year-old girl presented with presumed OHVIRA syndrome and had surgical correction of the obstructed hemivagina. Two years later she presented with increasing pelvic pain and underwent laparoscopy for presumed endometriosis. A single uterus with a broad flat fundus was found as well as endometriosis. CONCLUSION(S) OHVIRA syndrome is typically associated with a didelphys uterus with two cervices and two vaginas, one of which is obstructed. The obstruction usually occurs on the same side as the renal anomaly. We report a rare congenital anomaly of the female reproductive tract: OHVIRA syndrome with a single uterus. From a fertility standpoint, cases of a single uterus with two cervices are managed differently than two uteri with two cervices. Healthcare providers managing complex reproductive tract anomalies should be aware of this potential variant.

Scientific Investigation of Endometriosis among Adolescents

The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. It is possible that the disease has a different pathophysiology in adolescents, but little epidemiologic or molecular data exist to support or refute this speculation. In addition, the limited literature does not yet confirm that intervening in the adolescent population prevents long-term sequelae such as pain and infertility as adults. Case-control and cohort studies to identify risk factors, as well as prospective observational and intervention studies to assess treatment outcome, are required to further knowledge about endometriosis in the adolescent population. The scientific literature on endometriosis specific to the adolescent population is limited, and the existing data are retrospective and descriptive in nature. This review summarizes studies that have been done to date and suggests areas for future investigation.

Is breast always best?: a personal reflection on the challenges of breastfeeding.

My journey as a physician started 12 years ago. My journey as an infertility patient began far more recently—midway, ironically, through my own fellowship training in Reproductive Endocrinology and Infertility. In a surreal role reversal, I found myself sitting on the other side of the very desk that I counseled patients from, waving to my anesthesia colleagues as I was rolled in to the operating room, and ultimately in a hospital gown on the same in vitro fertilization unit where I had worked just the weekend before. After two in vitro fertilization cycles, I was pregnant. Forty-one weeks and one postdates induction later, I delivered a healthy baby girl. Given our difficulty in conceiving, I was grateful for the relative ease of the pregnancy and delivery, and was looking forward to the immediate “skin-toskin” contact I had been taught would facilitate breastfeeding. The joy I had anticipated when my daughter latched on, however, was replaced by searing pain. It was normal, I was told, my breasts just needed to “toughen up.” Two days later, I was still shouting expletives through every feed, and the baby had lost more than 15% of her body weight. I was told she had a tight frenulum, or “tongue tie,” that was causing a painful, ineffective latch. The pediatric otolaryngology fellow performed a frenulectomy the next day— and although my pain improved, my milk production did not. The hospital pediatricians instructed me to supplement with formula. Before I could do so, our hospital asked me to sign a release stating that I knew that breast milk is the very best form of nutrition but that I had nonetheless chosen to deviate from the practice of exclusive breastfeeding. I cried as I signed the form, feeling like I had let my baby down before even taking her home from the hospital. The next several weeks were a haze of lactation consultants, homeopathic remedies, and well-meaning advice. I chugged water. I popped fenugreek tablets. I filled a prescription for Reglan. I nursed until the baby screamed and beat my chest, then bottle-fed, then pumped—a process that took upwards of an hour, thereby putting me about 30 minutes away from having to repeat it again. The baby inhaled 3 ounces of formula every 2 hours, and my family celebrated when I was able to express a single ounce. As my tears and sleep deprivation continued, so did the feelings of perpetual inadequacy. Hundreds of thousands of women become pregnant every day, and yet I could not. Thousands more breastfeed their infants, and I could not. I chronicled each event as a series of failures that all pointed toward the same humiliating conclusion—I was not physiologically cut out to be a mother. The American Academy of Pediatrics’ (AAP) 2012 guidelines recommend exclusive breastfeeding for 6 months, followed by continued breastfeeding for 1 year or longer if mutually desired by mother and child. The AAP goes on to affirm that infant feeding should not be considered a lifestyle choice but rather a basic health issue. Both the general public and the medical community have embraced this recommendation. The American College of Obstetricians and Gynecologists calls on its fellows to support women in choosing to breastfeed their children. The World Health Organization and the United Nations Children’s Fund sponsor the Baby-Friendly Hospital Initiative to encourage and recognize hospitals that offer an optimal level of care for breastfeeding infants. The lay press is replete with articles that detail the benefits of breastfeeding for both mother and child. From the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.