Gad Liberty

Relationships between FSH, inhibin B, anti-Mullerian hormone, and testosterone during long-term treatment with the GnRH-agonist histrelin in patients with prostate cancer

OBJECTIVES Medical castration with long-acting GnRH-agonist (GnRHa) is a well-established treatment for metastatic prostate cancer. Our aim was to explore the relationships between FSH, inhibin B, anti-Mullerian hormone (AMH), and testosterone during treatment with an implant releasing GnRHa. DESIGN Analysis of hormone levels in frozen serum samples. METHODS Ten patients aged 77+/-7 (means+/-S.E.M.) years with prostate cancer were treated with the GnRHa histrelin for at least a year. Two weeks prior to insertion and for 3-4 months following removal the patients were treated with the antiandrogen flutamide. Serum inhibin B, FSH, testosterone, and AMH levels were measured retrospectively. RESULTS FSH, inhibin B, and testosterone increased during antiandrogen administration and levels fell after implant insertion. Four weeks post insertion, FSH gradually increased while inhibin B and testosterone remained fully suppressed. AMH levels did not change during antiandrogen treatment, but increased following implant insertion and remained elevated for the duration of implant use. Following removal, FSH and testosterone increased, inhibin B remained low, while AMH decreased. CONCLUSIONS The secondary increase in FSH following initial suppression with the implant is probably related to impaired inhibin B secretion. The lack of inhibin B response to the secondary increase in FSH suggests that long-term exposure of Sertoli-cells to GnRHa impairs their function. This effect appears to be selective since unlike inhibin B, AMH increased. In the absence of testosterone, FSH has a role in AMH regulation.

Ovarian hemorrhage after transvaginal ultrasonographically guided oocyte aspiration: a potentially catastrophic and not so rare complication among lean patients with polycystic ovary syndrome

OBJECTIVE To report the first case series of ovarian hemorrhage after transvaginal ultrasonographically guided oocyte aspiration (TVOA). DESIGN Retrospective analysis. SETTING In vitro fertilization unit of a tertiary university hospital. PATIENT(S) Patients who underwent TVOA during a 6-year period. INTERVENTION(S) Surgical intervention due to active bleeding from the ovary. MAIN OUTCOME MEASURE(S) Prevalence and risk factors. RESULT(S) Among 3,241 patients undergoing TVOA, 7 were diagnosed as having ovarian hemorrhage afterward. All patients were thin, with a body mass index of 19-21 kg/m(2), and 4 had polycystic ovary syndrome (PCOS). The prevalence of ovarian bleeding among lean patients with PCOS was 4.5%. The odds ratio for bleeding in lean patients with PCOS vs. all other patients was 50 (95% confidence interval 11-250). The interval between the TVOA and surgical intervention ranged from 5 to 18 hours (mean +/- SD, 11.4 +/- 5 hours). The Delta decrease in hemoglobin levels was 3.2-9 g/dL (mean 6.1 +/- 1.8). In 6 of the 7 patients, laparoscopically guided electrocoagulation was sufficient to achieve hemorrhagic control. CONCLUSION(S) Although acute hemorrhage is a rare event after TVOA, lean patients with PCOS specifically are at much higher risk for this complication.

Does day-3 LH/FSH ratio influence in vitro fertilization outcome in PCOS patients undergoing controlled ovarian hyperstimulation with different GnRH-analogue?

In an attempt to evaluate whether high basal day-3 luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio affects IVF cycle outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either GnRH-agonist (n = 47) or antagonist (n = 104), we studied 151 IVF cycles: 119 in patients with basal LH/FSH <2 and 32 in patients with LH/FSH ≥2. The PCOS with high LH/FSH ratio achieved a non-significantly higher pregnancy rate using the GnRH-agonist (50% vs 17.9%, p = 0.2; respectively), as compared to the GnRH-antagonist protocols, probably due to the ability of the long GnRH-agonist protocol to induce a prolong and sustained reduction of the high basal LH milieu and avert its detrimental effect on oocyte quality and implantation potential.

GnRH-agonist ovulation trigger in patients undergoing controlled ovarian hyperstimulation for IVF with ultrashort flare GnRH-agonist combined with multidose GnRH-antagonist protocol

Objective: To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH-agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH-antagonist (GnRH-ant) protocol is as effective as in patients at high risk to develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the multidose GnRH-ant protocol. Design: Cohort study. Setting: University hospital. Patients: All consecutive women aged ≤35 years admitted to our IVF unit from January 2011 to October 2011 who reached the ovum pick-up stage. Interventions: Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols. Main outcome measures: Ovarian stimulation characteristics, percentage of mature oocytes, fertilization and pregnancy rates. Results: No inbetween groups differences were observed in ovarian-stimulation related variable, percentage of mature oocytes, fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in the study, or the control groups. Conclusions: Three consecutive doses of daily GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH protocol, did not interfere with the ability of the GnRH-ag to trigger final oocytes maturation at the end of the COH cycle.

An upper limit of gonadotropin dose in patients undergoing ART should be advocated

Abstract Aim: As no upper limit of the daily dose of gonadotropins (DD GN) used for controlled ovarian hyperstimulation (COH) in patients undergoing assisted reproductive technology (ART) has been established, we aimed to evaluate the efficacy of using different DD GN in terms of live-birth achievement. Methods: Data of patients treated at a single university medical center during the same period was analyzed retrospectively. Four groups were analyzed according to the DD GN administered: group I (“high dose”):  >225– ≤ 375 IU; Group II (“Very high dose”): 376–450 IU; group III (“extremely high dose”): 451–600 IU. Normo-responders treated with DD GN ≤250 IU served as control (C). Variables included were DD GN, total GN dose/cycle, age, FSH, BMI, gravidity, parity, cycle number, IVF/ICSI, infertility diagnosis treatment protocol and outcome parameters. Results: The analysis of 1394 treatment cycles of 943 patients indicated that DD and total dose of GN correlated negatively with the number of oocytes, implantation, clinical pregnancy and live-birth rate (25.9%, 14.6%, 11.4% and 4.7% in groups C, I, II and III, respectively) The logistic regression analysis indicated that the adjusted odds ratios for LBR correlated inversely with the DD administered – independently from age, baseline FSH, BMI and previous failed cycles. Conclusions: Increasing the daily dose of GN to doses higher than 450 IU or a total dose of 3000 IU/cycle is at least questionable if not harmful.

Should high BMI be a reason for IVF treatment denial

Abstract Our aim was to examine the influence of BMI on the live-birth rate following IVF/ICSI and evaluate its specific contribution among other factors thus enabling accurate reproductive policy development. All patients that underwent IVF/ICSI at our center during January 2012–July 2015 were included in this retrospective study. A total of 1654 ICSI cycles were divided into four groups according to the patient’s BMI (kg/m2): group I (normal weight): <25 (943 cycles); group II (overweight): 25–30 (403 cycles); group III (obese): 30–35 (212 cycles); group IV (morbid obesity): >35 (96 cycles). Comparing the four groups of BMI, mean age and number of previous ART cycles was significantly lower in group I compared to groups II, III and IV. Length of treatment was significantly shorter in group I compared to groups II, III and IV. Ovarian response to COH was comparable in terms of mean estradiol and progesterone levels on the day of hCG administration mean number of oocytes retrieved, fertilized and number of embryos transferred. Endometrial thickness was significantly lower in group IV. Outcome measures, such as implantation rate, clinical pregnancy rate (CPR) per cycle and per ET, as well as live-birth rates did not differ significantly between the groups, although in group IV LBR per cycle and per ET was lower. Multivariate logistic regression stepwise analysis found a significant correlation between age and BMI but did not find correlation between BMI and clinical pregnancy (p = 0.436) or LB (p = 0.206). The results of our relatively large retrospective study did not demonstrate a significant impact of BMI on the ART cycle outcome. Therefore, BMI should not be a basis for IVF treatment denial.

Does progesterone to oocyte index have a predictive value for IVF outcome? A retrospective cohort and review of the literature

Abstract The potential adverse effect of Serum progesterone (SP) elevation on the day of hCG administration is a matter of continued debate. Our study aimed to evaluate the relative value of progesterone to a number of aspirated oocytes ratio (POI) to predict clinical pregnancy (CP) and live birth (LB) in fresh IVF cycles and to review the relevant literature. A retrospective analysis of GnRH Antagonist IVF-ET cycles. POI was calculated by dividing the SP on the day of hCG by the number of aspirated mature oocytes. A multivariate logistic regression analysis was performed to evaluate the predictive value of POI for CP and LB. Cycle outcome parameters included clinical pregnancy, live-birth and miscarriage. A total of 2,693 IVF/ICSI cycles were analyzed. POI was inversely associated with CP adjusted OR 0.063 (95% CI 0.016–0.249, p < .001) and with LB adjusted OR 0.036 (95% CI 0.007–0.199, p < .001). For prediction of LB, the area under the curve (AUC) was 0.68 (95% CI 0.64–0.71, p < .001) for the POI model. POI above the 90th percentile with a value of 0.36 ng/mL/oocyte results in CP and LB rates of 8.0 and 5.9%, respectively. POI is a simple index for the prediction of IVF-ET cycle outcomes, it can advocate a limit above which embryo transfer should be reconsidered.