Comparison of highly purified human menopausal gonadotropin and recombinant follicle stimulating hormone use in patients undergoing in vitro fertilization with progestin-primed ovarian stimulation protocol: a single center retrospective analysis.

PURPOSE: Recently, progesterone has been used to prevent LH surge instead of GnRH analogues during ART treatments, which is known as progesterone-primed ovarian stimulation (PPOS) protocol. During ART treatment, highly purified human menopausal gonadotropin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) are two of the agents used for stimulation of antral follicles. The aim of this study is to compare the efficacy and success of HP-hMG and rFSH agents in the ovarian stimulation step of the PPOS protocol, which has not been previously reported in the literature. METHODS: This retrospective study was conducted at a university hospital with patients who underwent IVF treatment using PPOS protocols in between January 2019 and July 2021. For ovarian stimulation, rFSH was used in group I and HP-hMG was used in group II. Mature oocyte ratio was the primary outcome, and live birth rate was the secondary outcome. Mann-Whitney and Chi-square tests were used for statistical analysis. All p values below 0.05 were considered significant. RESULTS: Total numbers of follicles, oocytes, MII, and 2PN numbers obtained were similar between the two groups. The fertilization rates were 66.7% in the rFSH group and 64.3% in the HP-hMG group (p > 0.05). The pregnancy rates were 53.5% and 46.7% in the rFSH and HP-hMG groups, respectively. There was no statistically significant difference between pregnancy, abortus, and live birth rates. CONCLUSION: In this study, it is demonstrated that stimulation of oocytes with either rFSH or hMG in the PPOS protocol, which has been added to IVF treatment protocols in recent years, had no statistical difference regarding mature oocyte numbers and live birth rates between the two groups. These results are consistent with the previous literature which compared rFSH and hMG in GnRH agonist and antagonist protocols.

Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes.

OBJECTIVE: To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. METHODS: A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. RESULTS: The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. CONCLUSIONS: The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Can AMH levels predict the need to step up FSH dose for controlled ovarian stimulation following a long GnRH agonist protocol in PCOS women?

BACKGROUND: To explore the role of anti-Mullerian hormone (AMH) in predicting the need to step up recombinant FSH (rFSH) dose following long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovarian syndrome (PCOS) women. METHODS: This is a retrospective cohort study of 825 PCOS women undergoing long GnRH agonist protocol enrolled from Jan 2019 to Dec 2021. The daily rFSH dose at which the first response to rFSH were recorded. The dose at which the first response to rFSH was based on folliculometry during follow up in which two or more follicles reached ≥ 11 mm. A receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict the need to step up initial rFSH dose. RESULTS: PCOS women who needed to step up initial rFSH dose had a significantly higher AMH compared with those didn't step up initial rFSH dose (11.37 ± 3.25ng/ml vs. 8.69 ± 3.16ng/ml, p < 0.001). In multivariate logistic regression analysis, increased AMH level was an independent factor for the need to step up initial rFSH dose in PCOS patients after adjusted for confounding factors. ROC curve analysis showed AMH could predict the need to step up initial rFSH dose (AUC = 0.738, 95%CI: 0.704-0.773), having 75.4% specificity and 63% sensitivity when the threshold AMH concentration was 9.30ng/ml. 58.8% PCOS women with AMH > 9.30 ng/ml required increased rFSH dose compared to 18.8% of women with AMH ≤ 9.30ng/ml (p < 0.001). Although the clinical pregnancy rate and live birth rate were not significantly different, there was a higher incidence of OHSS among women with AMH > 9.30 ng/ml vs. AMH ≤ 9.30ng/ml (20.8% vs. 15.3%, p = 0.043). CONCLUSION: PCOS women with AMH > 9.30 ng/ml were resistant to rFSH stimulation and require increased dose for the cycle recruitment of ovarian follicles.

Endometrial injury and rFSH before frozen-thawed embryo transfer: a case report.

Hormonal treatment as endometrial preparation for frozen-thawed embryo transfer (FET) is routinely carried out with oral, transdermal or combined estradiol supplementation; however, in some cases, there is no optimal endometrial development with this type of stimulation. In this case report, our patient failed to respond to conventional endometrial preparation techniques. For this reason, two unconventional techniques were combined to improve endometrial receptivity; endometrial injury, followed by rFSH administration. As a result of this combination, we achieved endometrium thickness, reaching 8.9 mm on day 15 of the cycle, carrying out the embryo transfer of two blastocysts on day-17 of the cycle, achieving clinical pregnancy and carrying it to completion with the birth of a baby.

A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose.

BACKGROUND: Since the first launch of a biosimilar recombinant follicle stimulating hormone (rFSH), Bemfola®, in Europe in 2014, it has been possible to study in routine clinical care throughout France the effectiveness of a biosimilar rFSH including according to different rFSH starting doses. METHODS: REOLA was a non-interventional, retrospective, real world study using anonymized data from 17 Assisted Reproductive Technology (ART) centres' data management systems across France including 2,319 ART ovarian stimulation cycles with Bemfola® and 4,287 ART ovarian stimulation cycles with Gonal-f®. For both products, four populations were studied according to starting dose of rFSH: < 150 IU, 150 - 224 IU, 225 - 299 IU and ≥ 300 IU. The primary endpoint was the cumulative live birth rate (cLBR) per commenced ART ovarian stimulation cycle including all subsequent fresh and frozen-thawed embryo transfers starting during a follow up period of at least 1 year following oocyte retrieval. RESULTS: A direct relationship of increasing rFSH starting dose with increasing age, increasing basal FSH, decreasing AMH and increasing body mass index was noted. No clinically relevant differences were seen in all outcomes reported, including the cLBR, between Bemfola® and Gonal-f®, but for both drugs, an association was seen with increasing rFSH starting dose and decreasing cLBR. CONCLUSIONS: The REOLA study demonstrates that the cLBR with Bemfola® is very similar to Gonal-f® across all patient subpopulations. The cLBR is inversely related to the rFSH starting dose irrespective of the drug used, and the REOLA study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting.

Considerations when treating male pubertal delay pharmacologically.

INTRODUCTION: Delayed puberty , usually affects psychosocial well-being. Patients and their parents show concern about genital development and stature. The condition is transient in most of the patients; nonetheless, the opportunity should not be missed to diagnose an underlying illness. AREAS COVERED: The etiologies of pubertal delay in males and their specific pharmacological therapies are discussed in this review. EXPERT OPINION: High-quality evidence addressing the best pharmacological therapy approach for each etiology of delayed puberty in males is scarce, and most of the current practice is based on small case series or unpublished experience. Male teenagers seeking attention for pubertal delay most probably benefit from medical treatment to avoid psychosocial distress. While watchful waiting is appropriate in 12- to 14-year-old boys when constitutional delay of growth and puberty (CGDP) is suspected, hormone replacement should not be delayed beyond the age of 14 years . When hypogonadism is diagnosed, hormone replacement should be proposed by the age of 12 years . Testosterone replacement has been used for decades and is fairly standardized. Aromatase inhibitors have arisen as an interesting alternative . Gonadotrophin therapy seems more physiological in patients with central hypogonadism, but its efficacy and timing still need to be established.

Overlapping biosimilar and originator follitropin alfa preparations: How much closer can they get?

Unfounded skepticism relating to biosimilars, arising from the assertion that they are not molecularly identical to their original counterpart, fails to acknowledge that no biological medicine, including Gonal-f® (from Merck Serono) is identical to itself. Molecular differences between the biosimilar and the reference medicines are irrelevant and clinically undetectable as long as they are contained within the accepted variability for the original medicine. Accordingly, the minor differences in 'ongoing pregnancy rate' and 'live birth' rate reported in a recent meta-analysis of biosimilars of Gonal-f® from Chua et al. are probably driven by product-unrelated factors, notwithstanding the fact that of the four products under analysis, only Ovaleap® (from Theramex UK Ltd) and Bemfola® (from Gedeon Richter Plc) can unambiguously be considered to be biosimilars. The EU Biosimilars model has proven successful, but some healthcare professionals, building on highly arguable premises, voice a distrust in biosimilars. Only if such scientifically unfounded distrust is reverted, the full promise of rFSH alfa biosimilars for reproductive medicine patients is likely to be fulfilled.

Evaluation of Controlled Ovarian Stimulation Protocols in Patients with Normal and Low Ovarian Reserve: Analyses of miRNAs and Selected Target Genes Involved in the Proliferation of Human Cumulus Cells and Oocyte Quality.

The oocyte and the surrounding cumulus cells (CCs) are deeply linked by a complex bidirectional cross-talk. In this light, the molecular analysis of the CCs is nowadays considered to be precious in providing information on oocyte quality. It is now clear that miRNAs play a key role in several ovarian functions, such as folliculogenesis, steroidogenesis, and ovulation. Thus, in this study, specific miRNAs, together with their target genes, were selected and investigated in CCs to assess the response of patients with normal (NR) and low (LR) ovarian reserve to two different controlled ovarian stimulation (COS) protocols, based on rFSH and hMG. Moreover, a Fourier transform infrared microspectroscopy (FTIRM) analysis was performed to evaluate DNA conformational changes in CCs and to relate them with the two COS protocols. The results evidenced a modulation of the expression of miRNAs and related target genes involved in CCs' proliferation, in vasculogenesis, angiogenesis, genomic integrity, and oocyte quality, with different effects according to the ovarian reserve of patients. Moreover, the COS protocols determined differences in DNA conformation and the methylation state. In particular, the results clearly showed that treatment with rFSH is the most appropriate in NR patients with normal ovarian reserve, while treatment with hMG appears to be the most suitable in LR patients with low ovarian reserve.

Ovarian stimulation drugs alter the metabolite content of the growing follicle: in vivo spectroscopic evaluation of follicle fluid

Objective: To determine and compare metabolite content using magnetic resonance spectroscopy (MRS) of growing follicles in patients with polycystic ovary syndrome (PCOS) receiving recombinant follicle stimulating hormone (rFSH), clomiphene citrate (CC) or aromatase inhibitor (AI) for ovarian stimulation. Material and Methods: Thirty patients diagnosed with PCOS and infertility and scheduled for ovarian stimulation were divided by therapy, rFSH/CC/AI, into three equal groups. Five fertile cases were designated as the control group. When the follicle diameters reached 16-18 mm in each group, patients underwent MRS and the metabolite content of a dominant follicle was analyzed. N-acetylaspartate, lactate (Lac), creatine (Cr), and choline (Cho) metabolite levels in parts per million were measured in the spectra. Results: A ~three-fold decrease in dominant follicle Cho content was found in patients receiving CC compared to control subjects. Similarly, the dominant follicle Cho intensities of patients given rFSH and AI were noted to be significantly higher than those who received CC. Only dominant follicle Lac levels of the patients who received CC were found to be significantly higher than the other groups. Cr peak intensities of patients receiving CC were found to be approximately three times less than control subjects. Cr signal intensity was significantly higher in patients receiving rFSH or AI than in patients receiving CC. While two patients became pregnant in the CC group, three patients in the AI group and five patients in the rFSH group became pregnant. The main metabolites detected in patients who conceived in each group were Cho and Cr. In cases who could not conceive, while Lac and lipid signals increased, Cho and Cr signals decreased. Conclusion: Unlike CC, ovarian stimulation with rFSH or AI does not alter dominant follicle metabolite content. The developmental capacity of a growing egg may be determined non-invasively with MRS.

The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways-Insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement.

OBJECTIVE: To delineate the role of gonadotropins in male androgen biosynthesis pathways. DESIGN: Case-control study. PATIENTS AND MEASUREMENTS: Twenty five males with congenital hypogonadotropic hypogonadism (CHH) underwent hCG/rFSH and testosterone treatment sequentially. Serum steroid hormone profiles (testosterone precursors and metabolites) on both replacement regimens were analysed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared to those of healthy controls, matched by age, BMI and serum testosterone. RESULTS: On testosterone replacement, serum concentrations of the classic Δ4 pathway hormones progesterone and 17-hydroxy-progesterone (17-OHP), and the marker steroid of an alternative pathway of testosterone synthesis (androstenediol) were decreased, compared to controls. Androstanediol, a marker of the backdoor pathway of dihydrotestosterone (DHT) synthesis, was increased. 17-OH-pregnenolone, androstenedione and DHEAS (Δ5 pathway), three 11-oxygenated C19 androgens (11-keto-A4, 11-keto-T and 11-keto-DHT) and the testosterone (T) metabolites DHT and 17ß-oestradiol (E2) were similar to controls. On gonadotropin replacement, 17-OHP, 17-OH-pregnenolone, DHEAS and androstenedione, as well as DHT, androstenediol, and all 11-oxygenated C19 androgens were normal. Progesterone (Δ4 pathway) was slightly decreased, and androstanediol (backdoor DHT pathway) and E2 (T metabolite) were increased. CONCLUSIONS: In males with CHH, serum steroid hormone profiles resemble those of healthy men, if hCG/rFSH is used for substitution. Gonadotropins contribute to steroid hormone production along the classic Δ4 pathway and co-activate an alternative pathway of testosterone biosynthesis via androstenediol. Backdoor DHT biosynthesis, Δ5 17-OH-pregnenolone, DHEA(S) and androstenedione synthesis and 11-oxygenated C19 androgen production are activated independently of gonadotropins. The androgen replacement modality used for treatment of hypogonadal males with absent or reduced endogenous LH/FSH secretion may impact on long-term health and quality of life.

Randomized controlled trial comparing embryonic quality in rFSH versus hMG in the IVF protocol with GnRH Antagonist.

OBJECTIVE: The aim of the present study is to investigate embryo quality (score) after controlled ovarian stimulation for IVF using rFSH or hMG with the GnRH antagonist protocol. METHODS: Open, randomized, single center study. The patients were randomized to receive rFSH or hMG according to randomized cards inside a black envelope with the name of the respective treatment following a computer generated list (85 patients were allocated to rFSH group and 83 patients to hMG group). Inclusion criteria were patients with IVF indication and normal ovarian reserve. Embryo evaluation was performed on day three, after fertilization based on the Graduated Embryo Score (GES). RESULTS: There were no relevant differences in demographic characteristics. There was no difference in pregnancy rates with 27 (31%) and 25 (30.1%) pregnancies for rFSH and hMG, respectively (p=0.87). The total embryo score was the same for both groups, but the best embryo score was significant higher for the rFSH group (77.33±34.0 x 65.07±33.2 p=0.03). The total number of embryos was statistical different, also in favor of the rFSH group (4.17±3.1 x 3.26±2.4 p=0.04). CONCLUSION: The total embryo score was the same for both groups, but the best embryo score was significantly higher for the rFSH group. Moreover, rFSH was associated with an increased number of embryos.

AMH-based ovarian stimulation versus conventional ovarian stimulation for IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: Anti-Müllerian hormone (AMH) used to establish patient profiles and predict ovarian response to stimulation, its role in assisted reproductive technology techniques is crucial. PURPOSE: To evaluate the evidence from published RCTs about the efficacy and safety of AMH-based ovarian stimulation versus conventional ovarian stimulation. METHOD: Search strategy: electronic databases were searched using the following MeSH terms (Anti-Müllerian hormone OR AMH) AND (IVF OR ICSI) and (tailored OR based). SELECTION CRITERIA: only RCTs were included. Four studies were included in the quantitative synthesis. DATA COLLECTION AND ANALYSIS: the extracted data were entered into RevMan software, the relative risk (RR) and 95% confidence interval (CI) were used for data analysis. RESULTS: Primary outcomes: ongoing pregnancy: test for overall effect was in favor of AMH-based group, but there was no statistically significant difference [RR = 0.95, 95% CI (0.84-1.08), P = 0.44]. Severe ovarian hyperstimulation syndrome (OHSS) test or overall effect was in favor of AMH-based group, but there was still no statistically significant difference [RR = 0.68, 95% CI (0.43-1.06), P = 0.09]. Secondary outcomes were dose of rFSH, the number of oocytes retrieved, fertilized oocytes, embryos (day 3), blastocysts (day 5), and duration of stimulation. Only the dose of rFSH and duration of stimulation were in the favor of AMH-based group, with statistically significant difference. The other four secondary outcomes were in the favor of the conventional group but with no statistically significant difference. CONCLUSION: AMH-based stimulation has the same results of pregnancy rate and risk of OHSS and can reduce the dose of rFSH and duration of stimulation.

Mild starting dosage ovarian stimulation combined with a modified prolonged GnRH-a protocol improved IVF/ICSI outcomes in normal ovarian responders.

INTRODUCTION: Controlled ovarian hyperstimulation (COH) is essential for artificial reproduction technology (ART). This study aimed to evaluate the effects of a mild starting dosage of r-FSH ovarian stimulation after the modified prolonged GnRH-a down-regulation protocol for COH on the clinical outcomes in normal ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). MATERIAL AND METHODS: In the retrospective study, the patients were separated into two groups according to the starting dosage of r-FSH: a mild dosage group (75 IU ≤ r-FSH < 150 IU, n = 858) and a conventional dosage group (150 IU ≤ r-FSH ≤ 225 IU, n = 535). Data were collected from clinical records. The baseline characteristics and clinical outcomes were compared between the two groups. RESULTS: Although the duration of r-FSH treatment was a little longer in the mild dosage group, the total r-FSH dosage and the cost of ovarian stimulation were significantly lower than those in the conventional dosage group. Furthermore, compared to the conventional dosage group, the number of retrieved oocytes was also lower in the mild dosage group, whereas the rates of two pronuclei (2PN) fertilized oocytes and good-quality embryos were remarkable higher. The implantation rate, clinical pregnancy rate and live birth rate were significantly higher in the mild dosage group. There was no difference in early miscarriages rate, incidence of moderate and severe ovarian hyper-stimulation syndrome (OHSS) or incidence of ectopic pregnancy between the two groups. CONCLUSIONS: The modified prolonged GnRH-a pituitary down-regulation regimen combined with mild r-FSH starting dosage improved IVF/ICSI outcomes and reduced the financial cost in normal ovarian responders.

Corifollitropin- α compared to daily r-FSH in for patients undergoing intracytoplasmic sperm injection: Clinical trial study.

BACKGROUND: The current treatment regimen for ovarian stimulation in Intracytoplasmic sperm injection (ICSI) patients is daily injections of Gonadotropins. Recombinant DNA technologies have produced a new recombinant molecule that is a long-acting Follicle Stimulating Hormone (FSH), named corifollitropin alfa. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled ovarian stimulation (COS) and can make assisted reproduction more patients-friendly. There is limited data with different results in this area. OBJECTIVE: To compare the effectiveness of long-acting FSH vs. daily r-FSH in terms of pregnancy and safety outcomes in women undergoing ICSI cycles. MATERIALS AND METHODS: In this clinical trial study, 109 women who were the candidates for ICSI at azzahra hospital were divided in two groups. The first group received 150 units of daily Gonal-f from second or third day of menstruation. The second group received a 150IU corifollitropin alfa on the second or third day of mensuration, and the treatment continued from day eighth of stimulation with Gonal-f based on the ultrasound finding. Both the groups received GnRH antagonist from fifth day of stimulation. Two groups were compared in terms of number of dominant follicles, number of oocytes, stimulation duration, total number of embryos, number of transferred embryos, and success rate of pregnancy. RESULTS: No significant difference was found between the two groups in terms of stimulation duration, number of follicles, number of oocytes, total number of embryos, and number of transferred embryos. Moreover, pregnancy outcomes including chemical pregnancy rate (positive pregnancy test), clinical pregnancy rate (detection of fetal heart), the rate of ovarian hyper-stimulation syndrome, multiple-pregnancy, ectopic pregnancy, and miscarriage didn't have a significant difference between the two groups. CONCLUSION: As corifollitropin alfa was as effective as r-FSH, it could be used as an alternative to ovulation stimulation method in patients undergoing ICSI.

Clinical outcomes following long GnRHa ovarian stimulation with highly purified human menopausal gonadotropin plus rFSH or rFSH in patients undergoing in vitro fertilization-embryo transfer: a multi-center randomized controlled trial.

BACKGROUND: This clinical trial aimed to compare the clinical efficacy of highly purified human menopausal gonadotropin (HP-HMG) plus recombinant human follicle-stimulating hormone (rFSH) versus rFSH alone on controlled ovarian stimulation (COS) in vitro fertilization-embryo transfer (IVF-ET). METHODS: A total of 610 women underwent long gonadotropin-releasing hormone (GnRH) agonist protocol for IVF treatment. The subjects were randomized into 2 groups: HP-HMG + rFSH group (n=305) and rFSH group (n=305). The main outcome was the progesterone (P) level on the day of HCG injection. RESULTS: There was no significant difference in terms of the demographic and baseline characters between the two groups. In rFSH group, the P level on the day of HCG trigger were significantly higher than that of HP-HMG+rFSH group (4.3±2.2 vs. 3.8±1.7 nmol/L, P<0.001). The fertilization rate in rFSH group was significantly lower than that of HP-HMG + rFSH group (69.2% vs. 73.9%, P<0.001). Simultaneously, the percentage of cycles with fresh embryo transfer in rFSH group was also significantly lower than that of HP-HMG + rFSH group (49.6% vs. 57.5%, P=0.007). However, there was no difference in terms of cleavage rate, implantation rate, clinical pregnancy rate and ovarian hyperstimulation syndrome (OHSS) rate between two groups. CONCLUSIONS: The use of combined HP-HMG with FSH may be superior to rFSH alone in stimulating the ovary in normal responders undergoing IVF treatment. Furthermore, the further prospective studies with large sample are still needed to confirm the study.

The impact of adding hp-hMG in r-FSH started GnRH antagonist cycles on ART outcome.

While luteinizing hormone (LH) activity is believed to play a role in follicle maturation, human chorionic gonadotropin (hCG) might play an important role in implantation process. We aimed to investigate whether addition of human menopausal gonadotropin (hMG) in recombinant-follicle-stimulating hormone (r-FSH) started GnRH antagonist controlled ovarian hyperstimulation (COH) cycles might enhance implantation rate and improve in vitro fertilization (IVF) success. A total of 246 patients undergoing GnRH antagonist IVF cycles were analyzed. One hundred and twenty-three cycles (%50) were treated with only r-FSH and 123 cycles were treated with r-FSH plus hp-hMG combination. Total gonadotropin doses, total number of oocytes retrieved, metaphase 2 (MII) oocytes, top quality embryos, fertilization and implantation rates, clinical pregnancy rates (CPRs) and ovarian hyperstimulation syndrome (OHSS) rates were compared between the groups. Both groups were comparable in terms of demographic details and baseline characteristics. Peak estradiol and progesterone levels in hCG trigger day, number of retrieved oocytes and top quality embryo counts, fertilization rates were similar between the groups. In r-FSH + hp-hMG group, significantly higher implantation rates (35.3% vs 24.3%, p=.017), CPRs (51.2% vs 35.8%, p=.015) and lower OHSS rates (1.6% vs 7.4%, p = .03) were observed respectively compared to r-FSH only treated patients. In conclusion, addition of hp-hMG on the day of antagonist initiation might increase CPRs. A better endometrial receptivity associated with higher implantation rates might be achieved due to hCG component in hp-hMG.

PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation.

PURPOSE: The present study aimed to determine clinical IVF parameters and gene expression in cumulus cells (CCs) in obese and normal weighting women after administration of 150 mcg of corifollitropin alfa for controlled ovarian hyperstimulation (COH). METHODS: 150 mcg of corifollitropin alfa and gonadotropin releasing hormone antagonist were used for COH. Analysis of CC gene expression was performed using quantitative real-time PCR. RESULTS: We did not find significant differences in biochemical and clinical pregnancy rates between obese and normal weighting women. Obese women required twice as much of additional gonadotropins for ovarian stimulation and had a significantly lower proportion of good quality embryos on day 5 of IVF cycle. Expression of PGR and PTX3 was significantly higher in CCs of obese women. CONCLUSION: Obese women require significantly larger amounts of gonadotropins to achieve similar IVF success rates as normal weighting women. Differences in CC gene expression and smaller proportion of good quality embryos may imply that oocytes derived from obese women are of lower quality. Further studies are needed to evaluate whether obesity itself or the higher amount of gonadotropins used in obese women causes this effect.

Management of hypogonadism from birth to adolescence.

Management of patients with hypogonadism is dependent on the underlying cause. Whilst functional hypogonadism presenting as delayed puberty in adolescence is relatively common, permanent hypogonadism presenting in infancy or adolescence is unusual. The main differential diagnoses of delayed puberty include self-limited delayed puberty (DP), idiopathic hypogonadotropic hypogonadism (IHH) and hypergonadotropic hypogonadism. Treatment of self-limited DP involves expectant observation or short courses of low dose sex steroid supplementation. More complex and involved management is required in permanent hypogonadism to achieve both development of secondary sexual characteristics and to maximize the potential for fertility. This review will cover the options for management involving sex steroid or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatment options.

The influence of ovarian hyperstimulation drugs on morphometry and morphology of human oocytes in ICSI program.

OBJECTIVE: To compare the influences of controlled ovarian hyperstimulation (COH) drugs using recombinant follicular stimulating hormone (rFSH) versus human menopausal gonadotropins (hMG) on morphometry and morphology of MII oocytes in ICSI cycles. MATERIALS AND METHODS: In this prospective study, 363 MII oocytes from 50 ICSI cycles with male factor infertility were evaluated. The patients were divided into two groups according to the protocols of COH: I- rFSH and II- hMG. The immature oocytes were excluded from the study. All oocytes were categorized into four morphological groups of normal, and those with single, double, or multiple defects. The inclusive morphometrical criteria were: areas and diameters of oocyte, ooplasm, and zona pellucida (ZP). Also, circumferences of oocyte and ooplasm were assessed. RESULTS: The ZP area and ooplasm diameter for both normal and abnormal oocytes were significantly higher in group I (P: .05; P: .028, respectively) compared to group II (P: .023; P: .003, respectively). In abnormal oocytes, ooplasm diameter was higher in group I compared to group II. Furthermore, ooplasm area for abnormal oocytes was significantly higher in group I compared to group II. There was an increasing trend for number of mature oocytes, in abnormal oocytes, for group I (5.53 ± 3.1) in comparison with group II (4.4 ± 2.97; P = .25). The rate of oocytes with normal morphology was significantly higher in hMG, when compared to rFSH groups. CONCLUSION: Morphometrical parameters were increased in rFSH group, but the normal morphology of oocytes were significantly enhanced in hMG group. Treatment with proper dosage of ovulation induction drugs may enhance the number of normal sized oocytes.

rFSH in medically assisted procreation: Evidence for ovarian follicular hyperplasia and interest of mass spectrometry to measure 17-hydroxyprogesterone and Δ4-androstenedione in serum.

Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens. At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314-585 pmol/L), estrone (165-379 pmol/L) testosterone (1.3-1.6 nmol/L), Δ4-androstenedione (4.5-5.6 nmol/L), 17-hydroxyprogesterone (2.1-2.2 nmol/L) and progesterone (1.8-1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.