Random anti-Müllerian hormone predicts ovarian response in women with high baseline follicle-stimulating hormone levels

Objective

To evaluate the predictive value of random serum anti-Müllerian hormone (AMH) in the assessment of ovarian response in patients with diminished ovarian reserve (DOR; diagnosed after the observation of elevated baseline levels of early follicular follicle-stimulating hormone [FSH]) who were undergoing intracytoplasmic sperm injection-embryo transfer (ICSI-ET) and to compare the random serum AMH and baseline FSH levels in these patients for the prediction of poor ovarian response.

Design

Retrospective study.

Setting

University hospital.

Patients

One hundred and thirty-nine patients who were undergoing ICSI-ET cycles with early follicular FSH level >9 IU/mL.

Intervention(s)

None.

Main Outcome Measure(s)

Poor ovarian response in ICSI-ET cycles.

Results

For the identification of women at risk of cycle cancellation, an AMH cut-off level ≤1.2 ng/mL had 97.3 % sensitivity, 31.3 % specificity, 33.9 % positive predictive value, and 96.9 % negative predictive value in the women with high baseline FSH levels. An AMH cut-off level ≥1 ng/mL had a sensitivity of 58.7 % and specificity of 95.1 % for prediction of retrieval of 4 or more oocytes. By using a serum AMH cutoff level of 1.5 ng/mL, the ongoing pregnancies were predicted with 83.3 % sensitivity and 82.5 % specificity and yielded a positive predictive value of 31.2 % and a negative predictive value 98.1 %.

Conclusion

Measurement of random serum AMH level is a useful tool in the prediction of ovarian response in patients with high serum early follicular FSH levels.     

A novel oocyte maturation trigger using 1500 IU of human chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease ovarian hyperstimulation syndrome across all in vitro fertilization stimulation protocols

Purpose

Modification of the trigger used to induce final oocyte maturation in in vitro fertilization (IVF) is a major strategy used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). A novel trigger composed of 1500 IU of human chorionic gonadotropin (hCG) plus 450 IU of follicle-stimulating hormone (FSH) has been developed to reduce OHSS risk. This study compares outcomes of the novel trigger to conventional triggers used in high-risk OHSS patients undergoing IVF.

Methods

In this retrospective cohort study, IVF cycles at high risk for OHSS based on a serum estradiol > 5000 pg/ml on trigger day conducted between January 2008 and February 2016 were evaluated. Oocyte maturation was induced with the novel trigger (1500 IU hCG plus 450 IU FSH) or a conventional trigger [3300 IU hCG, gonadotropin-releasing hormone agonist (GnRHa) alone, or GnRHa plus 1500 IU hCG]. IVF cycle outcomes were compared. Trigger strategies were examined for associations with OHSS development using logistic regression.

Results

Among 298 eligible IVF cycles identified, there were no differences in oocyte maturation, fertilization, embryo quality, or pregnancy outcomes among all triggers. After adjusting for serum estradiol level and number of follicles, the novel trigger was associated with lower odds of OHSS symptom development compared to the 3300 IU hCG and GnRHa plus hCG 1500 IU triggers (p = 0.007 and 0.04, respectively).

Conclusions

This study suggests that 1500 IU hCG plus 450 IU FSH may be associated with decreased OHSS symptoms compared to conventional triggers, while producing similar IVF and pregnancy outcomes. More important, this novel trigger may provide a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized.

     

Each baby counts in 2018 – lessons learned and future directions

The Royal College of Obstetricians and Gynaecologists (RCOG) launched the Each Baby Counts (EBC) project in 2015. The aim of the project is to reduce the number of stillbirths, early neonatal deaths and severe brain injuries in term babies born following labour by 50% by the year 2020. The first full report focussed on the quality of local reviews, fetal monitoring, individual human factors and neonatal care. For this article we have not focussed on the neonatal issues but have summarized the main points from each chapter. The aim of EBC will be achieved by focusing on three themes: (i) improving the quality of reviews of these babies, prompting local units to address their systematic failings that led to the outcome; (ii) development of toolkits and resources to support units to implement the recommendations in the report; (iii) improving care by establishing a platform for shared learning between units in order to adopt a more proactive approach to reducing babies who are harmed during labour.     

Elevated serum thyroid-stimulating hormone is associated with decreased anti-Müllerian hormone in infertile women of reproductive age

Purpose

Thyroid dysfunction and autoimmune thyroiditis are associated with fertility in women of reproductive age. Anti-Müllerian hormone (AMH), a known biomarker of ovarian function, may be affected by impaired thyroid function; however, the relationship between AMH and thyroid hormone has not been elucidated.

Methods

In this case–control study, to identify the impact of thyroid hormone on ovarian reserve, we recruited 67 consecutive Japanese infertile patients and 27 normal fertile women aged 30–39 years without impact factors on thyroid and ovarian functions between 2012 and 2013. We assessed patient age, BMI and AMH, prolactin, TSH and FT4 levels of all study participations as independent variables. To evaluate the relationship between AMH and thyroid hormone, we matched patients by age and body mass index as confounding factors using 1:1 matching for statistical analysis of healthy fertile women and infertile patients and obtained 23 pairs. Then, independent variables were subjected to multiple regression analysis.

Results

Multiple regression analysis showed that both thyroid-stimulating hormone (TSH) levels and patient age were negatively correlated with AMH levels in infertile patients (patient age and TSH: standardized partial regression coefficient (β), −0.534 and −0.361; p = 0.003 and 0.036, respectively), but not in normal fertile women.

Conclusions

AMH levels were inversely correlated with TSH levels in infertile women of reproductive age.     

The effect of different hormone therapies on anti-müllerian hormone serum levels in anovulatory women of reproductive age

Objective.?To investigate the effect of oral contraceptives (OC), metformin and ovulation induction with gonadotropins on circulating anti-müllerian hormone (AMH).

Design.?Prospective clinical study.

Patients.?Thirty patients with PCOS (Group 1), 15 normogonadotropic anovulatory infertile women (WHO 2) (Group 2) and 15 normoovulatory control women (Group 3). Patients in Group 1 received OC (n?=?12), metformin (n?=?11) or no-treatment (n?=?7) for 6 months. Ovulation induction with FSH or hMG was used in Group 2.

Main outcome measures.?Total follicle number (TFN) and hormonal (fasting insulin and glucose, testosterone, SHBG, LH, androstenedione and AMH) measurements at baseline and during therapy.

Results.?Basal AMH and TFN were higher in Groups 1 and 2 than in controls. Only TFN was significantly related to AMH level in Groups 1 and 2. AMH level was significantly reduced during OC treatment, and there was a trend for AMH decrease during metformin therapy. No significant changes in AMH level were observed during ovulation induction. TFN was the only parameter showing a significant positive correlation with circulating AMH over the 6-month treatment period in patients in Group 2.

Conclusions.?AMH is an accurate marker of the antral follicle pool in WHO-2/PCOS women but the measurement of AMH is not likely to be helpful in the management of those patients.     

Growth hormone: a reproductive endocrine-paracrine regulator?

Growth hormone (GH) is not classically considered as a reproductive hormone, although a vast literature indicates that it has roles in reproductive function. It is required for sexual differentiation and pubertal maturation and it participates in gonadal steroidogenesis, gametogenesis and ovulation. GH is also required for fetal nutrition and growth during pregnancy and for mammary development and lactation. Although some of these roles reflect the action of GH on the secretion and action of LH and FSH (Chandrashekar and Bartke, 1998), they also reflect direct actions of GH and indirect actions mediated through the local production of insulin-like growth factor I. Moreover, as GH is produced in gonadal and mammary tissues, these actions may reflect local autocrine or paracrine actions of extrapituitary GH, as well as the endocrine actions of pituitary GH. The roles of GH in reproductive function are considered in this review.     

Estrogen receptor-β in the gonadotropin-releasing hormone neuron

Estrogen regulation of gonadotropin-releasing hormone (GnRH) neuronal activity plays a crucial role in homeostatic regulation of the hypothalamic-pituitary-gonadal axis. Estrogen also coordinates a complex series of physiological changes culminating with a surge of gonadotropin secretion that triggers ovulation of a developed follicle from the ovary. The coordinated functions of estrogen ensure that the female will elaborate appropriate reproductive behaviors ultimately designed to deliver sperm to the oocyte and to provide a receptive uterine environment for the fertilized embryo. Although the effects of estrogen on GnRH neuronal function have long been proposed to be indirect due to the presumed lack of estrogen receptors in GnRH neurons, the identification of alternative estrogen signaling pathways, including estrogen receptor (ER)β and membrane ERs such as GPR30, has put the focus back on estrogen's effect at the level of the GnRH neuron itself. One candidate to mediate the effects of estrogen is the β isoform of the estrogen receptor. We review the evidence for a role for ERβ-mediated regulation of GnRH neuronal function.     

When did leptin become a reproductive hormone?

Almost 50 years ago the obese mouse model was identified, and parabiosis studies were able to demonstrate that some humoral factor was involved in adiposity, so that the genetics and endocrine nature of this process have been apparent for many years. With the discovery of leptin just a few years ago, early studies validated the role of this protein product of the obese gene. Early studies in the obese mouse model ( ob/ob mouse) demonstrated that the genetic basis was truly a deficiency in leptin. Coincidentally, the relationship to fertility was also associated with leptin. These early studies were also able to demonstrate a relationship to puberty and the time of pubertal development. Very quickly, the recognition that the placenta was a source of leptin and that leptin levels were elevated in pregnancy in a number of species also broadened our appreciation of the relationship to reproductive functions. These many rapidly elucidated relationships to leptin were reported soon after the identification and availability of leptin as a research reagent and have firmly put leptin into the area of reproductive physiology in addition to establishing roles in metabolism, satiety, and energy metabolism. Subsequent studies have expanded all of these situations. Species beyond the rodent model, including the human, have now introduced these physiologic studies into the clinical arena and the role of leptin in fertility, puberty, pregnancy, and genetics. In this issue, all of these topics are reviewed to bring the reader up to date with leptin and its role in reproductive function, many of which overlap with the control of obesity.