Obesity and High-Fat Diet Induce Distinct Changes in Placental Gene Expression and Pregnancy Outcome.

Obese women are at high risk of pregnancy complications, including preeclampsia, miscarriage, preterm birth, stillbirth, and neonatal death. In the current study, we aimed to determine the effects of obesity on pregnancy outcome and placental gene expression in preclinical mouse models of genetic and nutritional obesity. The leptin receptor (LepR) null-reactivatable (LepRloxTB), LepR-deficient (Leprdb/+), and high-fat diet (HFD)-fed mice were assessed for fertility, pregnancy outcome, placental morphology, and placental transcriptome using standard quantitative polymerase chain reaction (qPCR) and qPCR arrays. The restoration of fertility of LepRloxTB was performed by stereotaxic delivery of adeno-associated virus-Cre into the hypothalamic ventral premammillary nucleus. Fertile LepRloxTB females were morbidly obese, whereas the wild-type mice-fed HFD showed only a mild increase in body weight. Approximately 80% of the LepRloxTB females had embryo resorptions (∼40% of the embryos). In HFD mice, the number of resorptions was not different from controls fed a regular diet. Placentas of resorbed embryos from obese mice displayed necrosis and inflammatory infiltrate in the labyrinth and changes in the expression of genes associated with angiogenesis and inflammation (e.g., Vegfa, Hif1a, Nfkbia, Tlr3, Tlr4). In contrast, placentas from embryos of females on HFD showed changes in a different set of genes, mostly associated with cellular growth and response to stress (e.g., Plg, Ang, Igf1, Igfbp1, Fgf2, Tgfb2, Serpinf1). Sexual dimorphism in gene expression was only apparent in placentas from obese LepRloxTB mice. Our findings indicate that an obese environment and HFD have distinct effects on pregnancy outcome and the placental transcriptome.

Biochemical and Imaging Diagnostics in Endocrinology: Predictors of Fertility.

One of the limiting factors of fertility testing is the relative inefficiency of human reproduction. A careful history and physical examination must be performed on each patient to inform the particular diagnostic tests that are chosen and to create a meaningful treatment plan. Testing parameters, such as sensitivity, specificity, positive predictive value, and negative predictive value, can help to interpret test results, although there is no perfect screening test for the various causes of infertility. This article describes the 4 major categories of testing for infertility: ovarian reserve, ovulatory status, gamete transport, and male factor.

AMPKα2 in Kiss1 Neurons Is Required for Reproductive Adaptations to Acute Metabolic Challenges in Adult Female Mice.

A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal axis is adaptive when energy reserves are diminished, allowing individual survival and energy accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor of the AMP to ATP ratio and ultimately of energy availability. Activation of AMPK suppresses ATP-consuming processes and stimulates ATP-producing pathways. The AMPK α2 catalytic subunit is expressed in multiple hypothalamic nuclei including those associated with reproductive control, ie, the anteroventral periventricular nucleus and the arcuate nucleus. Subsets of kisspeptin neurons in the anteroventral periventricular nucleus (20% in females) and arcuate nucleus (45% in males and 65% in females) coexpress AMPKα2 mRNA. Using the Cre-loxP approach, we assessed whether AMPKα2 in Kiss1 cells is required for body weight and reproductive function. The AMPKα2-deleted mice show no difference in body weight and time for sexual maturation compared with controls. Males and females are fertile and have normal litter size. The AMPKα2-deleted and control females have similar estradiol feedback responses and show no difference in Kiss1 mRNA expression after ovariectomy or ovariectomy plus estradiol replacement. In males, acute fasting decreased Kiss1 mRNA expression in both groups, but no effect was observed in females. However, after an acute fasting, control mice displayed prolonged diestrous phase, but AMPKα2-deleted females showed no disruption of estrous cycles. Our findings demonstrate that the AMPKα2 catalytic subunit in Kiss1 cells is dispensable for body weight and reproductive function in mice but is necessary for the reproductive adaptations to conditions of acute metabolic distress.

Fertility Preservation Decisions Among Newly Diagnosed Oncology Patients: A Single-Center Experience.

OBJECTIVES: To evaluate fertility preservation decisions and compare controlled ovarian stimulation (COS) and assisted reproductive technology (ART) outcomes between newly diagnosed cancer patients and age-matched healthy controls. METHODS: Our retrospective study was conducted at Columbia University's Center for Women's Reproductive Care between 2005 and 2012. Forty-nine women elected to undergo ART with COS for either oocyte or embryo cryopreservation before commencement of cancer therapy. Demographic and descriptive characteristics were collected from the cohort of patients. Treatment outcomes were compared with randomly selected, healthy, age-matched controls undergoing ART with COS during the same time period. RESULTS: Single women began fertility preservation cycles in half the time of married women (10.4 vs. 22.9 d). All 21 married women chose embryo cryopreservation, whereas 17 of the 28 (61%) single women chose embryo over oocyte cryopreservation. Baseline anti-Mullerian hormone levels and body mass indices were similar among fertility preservation patients and controls. Despite elevated baseline estradiol (E2) levels and luteal phase cycle starts in some cycles to avoid delay of cancer treatment, no significant differences were noted when comparing days of stimulation, total gonadotropins prescribed, numbers of oocytes and mature oocytes retrieved, fertilization rate, or cancellation rate to controls. CONCLUSIONS: Our experience shows that, with appropriate counseling and multidisciplinary care, newly diagnosed cancer patients desiring fertility preservation experience similar outcomes as age-matched healthy controls. These women can pursue oocyte or embryo cryopreservation with likely minimal disruption to the flow of their oncologic care.

Pregnancy despite ovarian insufficiency in a patient with breast cancer.

Future fertility is a concern for many young breast cancer survivors. Secondary amenorrhea occurs frequently during or soon after oncologic treatment. Return of menstruation and serum biomarkers are not absolute predictors of future fertility. We report a case of a 28 year old gravida 0 with recurrent Stage IIB invasive ductal breast carcinoma who managed to conceive twice despite showing clinical and biochemical signs of decreased ovarian reserve following treatment with chemotherapy and radiation. This case illustrates the potential for fertility in a patient with breast cancer despite chemotherapy-related amenorrhea and undetectable anti-Müllerian hormone levels. It exemplifies the imprecise nature of all clinical tests used to predict future fertility in breast cancer patients post-treatment. It should remind all providers to be careful in basing recommendations for childbearing on these surrogate endpoints.

Pregnancy after in vitro fertilization in a liver transplant patient.

We present the case of a liver transplant patient who conceived following assisted reproduction and experienced a normal pregnancy with a good outcome. This case illustrates that, in select cases and with multidisciplinary effort, women may undergo ovarian hyperstimulation and egg retrieval following liver transplant without undue risk or complications.