A randomized controlled trial comparing the efficacy and safety of two HMG preparations gaining their LH bioactivity from different HCG sources.

In this prospective, controlled, randomized, multicentre, non-inferiority study, efficacy and safety of two HMG preparations (Menopur®- Ferring and Meriofert®- IBSA Institut Biochimique SA) for ovarian stimulation were compared (270 women undergoing IVF aged between 18 and 39 years; BMI 30 kg/m2 or less; less than three prior completed assisted reproduction technique cycles). A standard long down-regulation with gonadotrophin-releasing hormone agonist protocol, with HCG triggering was used; primary end-point was total number of oocytes retrieved; attention was paid toovarian hyperstimulation syndrome (OHSS). No statistically significant differences between the treatment groups were reported for most of the clinically significant end-points, including embryo quality, fertilization rate, implantation rate, ongoing pregnancy rate and live birth rate. Total number of oocytes retrieved was higher in the new HMG group compared with the reference (11.6 ± 6.6 and 9.7 ± 5.9, respectively, with a 95% CI of the difference equal +0.43 to +3.43). Increased number of oocytes was obtained through a shorter stimulation, but HMG units per oocyte retrieved were equivalent. The safety profile of the products for frequency of ovarian hyperstimulation syndrome was the same. This study showed that the new HMG preparation is a viable alternative for conducting ovarian stimulation in IVF cycles.

Retrospective comparison of GnRH agonist trigger with HCG trigger in GnRH antagonist cycles in anticipated high-responders.

All IVF-ICSI cycles carried out between October 2009 and October 2012 using GnRH agonist (GnRHa) ovulation trigger (n = 62) followed by a single dose of HCG plus progesterone and oestradiol in the luteal phase because of anticipated ovarian hypertsimulation were retrospectively compared with historic control cycles using HCG trigger (n = 29) and standard luteal phase support. Women's mean age, body mass index, anti-Müllerian hormone, FSH, LH, starting and total stimulation dose, number of follicles, oocytes, embryos, fertilization, implantation, polycystic ovary syndrome, ICSI, live birth and ongoing pregnancy rates per embryo transfer were similar (GnRHa 40.7% versus HCG 35.0%). For each started cycle, GnRHa resulted in 11.4% higher (statistically non-significant) live birth and ongoing pregnancy rate (OR 1.73, CI 0.64 to 4.69), with a similar difference for double-embryo transfers (OR 1.62, CI 0.44 to 6.38) and less need for freezing all embryos (9.7% versus 27.6%; P = 0.04). Incidence of mild-to-moderate OHSS was 16.2% with GnRHa trigger and 31.0% with HCG trigger) and no severe OHSS in the former. The addition of single low-dose HCG in the luteal phase after GnRHa trigger for suspected high-responders reduced the incidence of OHSS with good clinical outcomes, compared with HCG trigger.

Circulating LH/hCG receptor (LHCGR) may identify pre-treatment IVF patients at risk of OHSS and poor implantation.

BACKGROUND: Successful pregnancy via in vitro fertilization (IVF) depends on the recovery of an adequate number of healthy oocytes and on blastocyst implantation following uterine transfer. Two hormones, LH and hCG, utilize a common LH/hCG receptor (LHCGR), variations in which have profound implications in human reproduction. Soluble LHCGR (sLHCGR) is released from experimental cell lines and placental explants and it can be detected in the follicular fluid and serum. METHODS: To evaluate the impact of circulating soluble LHCGR (sLHCGR) in fertility treatment, we measured sLHCGR and LH-sLHCGR complex in serum from women seeking IVF using specifically developed quantitative enzyme-linked immunosorbent assays (ELISA). Following an IVF cycle of treatment, patients were grouped according to oocyte yield into low (lower than or equal to 7 oocytes), intermediate (8-14 oocytes) and high (greater than or equal to 15 oocytes) responders and pregnancy outcome noted. RESULTS: Pre-treatment sLHCGR identified many women at risk of ovarian hyperstimulation. Low levels of sLHCGR were associated with pregnancy in both high and low responders but sLHCGR did not significantly affect the treatment outcome of intermediate responders. Low responders who failed to become pregnant had high levels of circulating sLHCGR bound to LH (LH-sLHCGR). CONCLUSIONS: Pre-treatment measurement of sLHCGR could be used to tailor individual fertility treatment programs and improve outcomes by avoiding ovarian hyperstimulation and poor embryo implantation.

Social egg freezing: the prospect of reproductive 'immortality' or a dangerous delusion?

Until recently there was little to offer young women with cancer facing chemotherapy, radiotherapy or surgery and the probability of premature menopause and sterility. The first 'frozen egg' baby was born in 1986, but success rates were so low that egg freezing was neglected. Three technological developments in assisted reproduction treatment (intracytoplasmic sperm injection, dehydro-cryoprotectants and vitrification) have transformed this picture and now young women with frozen eggs have the same probability of a live birth per embryo transfer as women undergoing conventional IVF. For many women it is not cancer but the passage of time that denies them a chance of motherhood. Social, educational and financial pressures often lead them to delay starting a family until their late thirties, by which time the chance of success is compromised by low fecundity rates and an increased risk of miscarriage if they become pregnant. Donor eggs are not an option for many because of supply constraints and ethical concerns. Freezing a woman's eggs at age 30 literally 'freezes in time' her fertility potential and gives her the chance of a healthy pregnancy at a time of her choosing. The role of oocyte cryopreservation in the context of social egg freezing is discussed. Until recently there was little we could offer young women with cancer facing the chemotherapy, radiotherapy or surgery that could save their lives and the certainty of premature menopause and sterility. The first frozen-egg baby was born in 1986, but the success rate (100 eggs to produce one baby) was so low that egg freezing was neglected for years. Three technological developments in assisted reproduction treatment (intracytoplasmic sperm injection, dehydro-cryoprotectants and vitrification) have transformed this picture and now young women who have cryopreserved eggs can be offered the same chance of a live birth per embryo transfer as women undergoing conventional IVF treatment. For many women today it is not cancer but the simple passage of time that robs them of their chance of motherhood. Social, educational, emotional and financial pressures often lead them to delay trying to start a family until their late thirties, by which time the chance of success is very low. Women at age 40 face a 40% chance of miscarriage if they can get pregnant at all and by the age of 45, the risk of miscarriage is 75%. Donor eggs are not an option for many because of supply constraints and ethical and cultural concerns. Freezing a woman's eggs at age 30 literally 'freezes in time' her fertility potential and gives her the chance of a healthy pregnancy at a time of her choosing. This paper discusses the role of oocyte cryopreservation in the context of social egg freezing.

Can we predict the chance of successful epididymal or testicular sperm aspiration following vasectomy?

Purpose of this retrospective study was to investigate if serum markers, men's age, interval since vasectomy, BMI, testicular size and smoking could predict the success of epididymal or testicular sperm aspiration (PESA/TESA) in vasectomized men. Forty-four consecutively performed PESA/TESA procedures were reviewed retrospectively. Motile sperm was retrieved from 77.3% of PESA/TESA procedures. Mean serum Inhibin-B (Inh-B) level tended to be higher in men who had motile sperm retrieved compared to those who had not (180.3 versus 126.2 pg/ml, p = 0.05). Univariate analysis identified serum Inh-B to be the only predictor of PESA/TESA success (r = 0.32, CI: 0.006-0.584, p = 0.046). Serum FSH, LH, T levels, age, BMI, smoking status and interval since vasectomy did not correlate with the PESA/TESA outcome. Inh-B could modestly discriminate between successful and unsuccessful PESA/TESA (AUC= 0.70) with high positive (89.5%) but low negative prediction (36.8%); 58.6% sensitivity and 77.7% specificity at the optimum cut-off level of 166 pg/ml. Positive outcome was only 50% when the Inh-B level was below 100 pg/ml. It is concluded that a high serum Inh-B might reliably predict successful PESA/TESA in vasectomized men. More invasive sperm retrieval procedures could be reserved for men with very low Inh-B or failed PESA/TESA. Future studies with adequate power may confirm our findings.

The diagnostic value of inhibin in infertility evaluation.

The fertility patient is entitled to a rapid and accurate diagnosis, a realistic assessment of the prospects for achieving pregnancy, and the timely initiation of an appropriate and effective therapy. The evaluation of ovarian reserve prior to initiation of ovarian stimulation is an important aspect of the infertility work-up of a woman requiring assisted reproductive techniques (ARTs). The ability of the ovary to respond to gonadotropin stimulation by the recruitment of a cohort of follicles is central to the success of treatment such as in vitro fertilization and intracytoplasmic sperm injection. Ovarian dysfunction, often age related, is an increasingly common cause of subfertility, and hyper- and hypogonadotropic dysovulation as well as the commoner polycystic ovarian syndrome (PCOS) are frequently encountered in fertility clinic. In cases of male-factor infertility, an ability to identify an accurate serum marker of Sertoli cell function has enhanced the diagnostic process, as previous endocrine markers such as follicle-stimulating hormone and testosterone were poor correlates of spermatogenic potential. The identification, purification, and cloning of the members of the inhibin-activin superfamily and the subsequent development of sensitive and highly specific two-site enzyme-linked immunoassays for these polypeptide hormones have provided tentative answers to many of the outstanding questions concerning the regulation of the hypothalamo-pituitary-gonadal axis. Assessment of serum levels of inhibin B appears to offer useful prognostic information about ovulatory function and predictive information about response to treatment. During very early pregnancy, especially in the presence of complications associated with ART such as multiple gestation and ovarian hyperstimulation syndrome, measurement of maternal levels of inhibin A and pro-alphaC offers a noninvasive test that can aid the counseling and management of patients.

Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study.

OBJECTIVE: To compare the safety, efficacy, and tolerability of subcutaneous progesterone (Prolutex, 25 mg; IBSA Institut Biochimique SA) with vaginal progesterone gel (Crinone, 8%; Merck Serono) for luteal phase support (LPS) in assisted reproduction technologies (ART) patients. DESIGN: Prospective, open-label, randomized, controlled, parallel-group, multicenter, two-arm, noninferiority study. SETTING: Thirteen European fertility clinics. PATIENT(S): A total of 683 ART patients randomized to two groups: Prolutex, 25 mg subcutaneously daily (n = 339); and Crinone, 90 mg 8% gel daily (n = 344). INTERVENTION(S): In vitro fertilization and embryo transfer were performed according to site-specific protocols. On the day of oocyte retrieval, Prolutex or Crinone gel was begun for LPS and continued for up to 10 weeks. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): The primary end point, ongoing pregnancy rates at 10 weeks of treatment were 27.4% and 30.5% in the Prolutex and Crinone groups, respectively (intention to treat [ITT]). The nonsignificant difference between the groups was -3.09% (95% confidence interval [CI] -9.91-3.73), indicating noninferiority of Prolutex to Crinone. Delivery and live birth rates resulted to be equivalent between the two treatments (26.8% vs. 29.9% in the Prolutex and Crinone groups, respectively [ITT]; difference -3.10 [95% CI -9.87-3.68]). No statistically significant differences were reported for any of the other secondary efficacy endpoints, including comfort of usage and overall satisfaction. CONCLUSION(S): Implantation rate, pregnancy rate, live birth rate, and early miscarriage rate for Prolutex were similar to those for Crinone. The adverse event profiles were similar and Prolutex was safe and well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: NCT00827983.

The role of inhibin in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its severest manifestations, is associated with anovulation, hyperandrogenism and metabolic imbalance. The biochemical markers for the condition can include a significantly raised LH:FSH ratio and a raised testosterone concentration, indicating a derangement of the hypothalamo--pituitary--ovarian axis which may be primary or secondary to a primary ovarian pathology. The bioactive inhibins are heterodimeric glycoproteins consisting of alpha-betaA (inhibin A) and alpha-betaB (inhibin B) subunits. They play an endocrine role in co-regulating (with oestradiol) the suppression of FSH during the late follicular and luteal phases of the ovarian cycle and they are implicated in intraovarian paracrine signalling. Inhibin B, which is the predominant form in small pre-ovulatory follicles, increases in concentration from early in the follicular phase to reach a peak coincident with the onset of the decrease in FSH which forms the basis of the pattern of mono-ovulation seen in normo-ovulatory women. Several unique features of the dysovulation of women with PCOS, namely their failure to recruit and develop a dominant follicle despite having 'normal' concentrations of endogenous FHS, the raised LH:FSH ratio and their exquisite sensitivity to exogenous FSH injections, may be explained by their significantly higher inhibin B concentrations. Studies into inhibin B parameters in women with PCOS demonstrate that women with anovular PCOS have significantly higher concentrations of circulating inhibin B and that they lack the pulsatile pattern of secretion that can be detected in normo-ovulatory women during the mid-follicular phase. The inhibin B response to ovulation induction with clomiphene citrate in women with PCOS differs from that in normo-ovulatory women taking the antioestrogen. Women with PCOS who over-respond to ovulation induction with injected FSH in a 'low-dose' step-up protocol' and recruit multiple follicles have significantly higher concentrations of pre-treatment inhibin B than PCOS subjects who do not.

Successful transvaginal ultrasound-guided ablation of a cervical pregnancy in a patient with simultaneous intrauterine pregnancy after in vitro fertilization and embryo transfer.

Heterotopic pregnancy, or simultaneous intrauterine and extrauterine gestation, is a relatively rare condition. However, induced ovulation and assisted reproductive technologies have markedly increased the incidence of this condition. In this article, a case of heterotopic pregnancy after in vitro fertilization and embryo transfer is presented in which the viable cervical pregnancy was treated by transvaginal ultrasound-guided puncture and injection of potassium chloride in conjunction with methotrexate at week 6 of gestation. At week 12 of gestation, the intrauterine gestation was viable and complete resorption of the cervical pregnancy had occurred. At week 30 of gestation, a healthy baby was delivered by Caesarian section after prelabour rupture of membranes.