Urinary Human Menopausal Gonadotropin Research Articles

Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial

BackgroundCurrently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist.MethodsIn this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically.ResultsThe statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004).ConclusionsOn the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk.Trial registrationNCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03876145.

Cost-effectiveness analysis of recombinant human follicle-stimulating hormone alfa(r-hFSH) and urinary highly purified menopausal gonadotropin (hMG) based on data from a large German registry.

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German invitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles.

The Reproductive Outcome of Women with Hypogonadotropic Hypogonadism in IVF.

ObjectiveThe purpose of this study was to evaluate the reproductive outcome of patients with hypogonadotropic hypogonadism (HH) receiving in vitro fertilization and embryo transfer (IVF-ET).MethodsThe reproductive outcome of 81 HH patients and 112 controls who underwent oocyte retrieval was evaluated retrospectively in the Center for Reproductive Medicine of Peking University Third Hospital from 2010 to 2019.ResultsThe basic levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), androstenedione (A) and prolactin (PRL) were significantly lower in the HH group than the control group. Although the HH patients required a significantly longer stimulation and higher gonadotropin (Gn) doses than the control patients, the total number of oocytes retrieved, fertilized embryos, two pronuclear (2PN) embryos, transferable embryos, fertilization and 2PN rates were comparable between the two groups. Although the live birth rate (LBR) of the first fresh cycle was higher in the control group than the HH group, there was no statistical significance. Then we further divided HH patients into two subgroups according to the etiology. Forty-one cases were termed as congenital HH (CHH), while the other 40 cases were termed as acquired HH (AHH), the latter includes functional hypothalamic amenorrhea (FHA) and pituitary HH (PHH). Our results showed that there were no significant differences in basic clinical characteristics and IVF parameters between the two groups. In the HH group, a total of 119 oocyte retrieval cycles were carried out and they responded adequately to ovulation induction. Urinary human menopausal gonadotropin (HMG) was used alone in 90 cycles while combination of HMG and recombinant human follicle stimulating hormone (rFSH) in the other 29 cycles. There were no significant differences in IVF-related parameters between the two groups. The conservative cumulative live birth rates (CLBRs) after the first, the second and ≥third cycles were 43.21%, 58.02% and 60.49%, respectively, while the corresponding optimal CLBRs were 43.21%, 68.45% and 74.19%. The preterm birth (PTB) rates of singletons and twin pregnancy in HH patients were 8.33% (3/36) and 30.77% (4/13), respectively.ConclusionIVF-ET is an effective treatment for HH patients with infertility and patients can get satisfactory pregnancy outcomes.

POSC109 Cost-Effectiveness Analysis of Reference Recombinant Human Follicle-Stimulating Hormone ALFA (R-HFSH-ALFA) and Urinary Highly Purified Menopausal Gonadotropin (HMG-HP) Based on DATA from a Large German Registry

To evaluate the real-world cumulative cost per live birth and cost-effectiveness (incremental cost-effectiveness ratio [ICER]) of reference recombinant human follicle-stimulating hormone-alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), for up to three cumulative assisted reproductive technologies (ART) cycles (maximum three stimulations and corresponding frozen-embryo transfers).

Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany

BackgroundThis study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany.MethodsData were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle).ResultsTwenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP.ConclusionsThis large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility.

The first commercially available gonadotropin product was a human chorionic gonadotropin (hCG) extract, followed by animal pituitary gonadotropin extracts. These extracts were effective, leading to the introduction of the two-step protocol, which involved ovarian stimulation using animal gonadotropins followed by ovulation triggering using hCG. However, ovarian response to animal gonadotropins was maintained for only a short period of time due to immune recognition. This prompted the development of human pituitary gonadotropins; however, supply problems, the risk for Creutzfeld–Jakob disease, and the advent of recombinant technology eventually led to the withdrawal of human pituitary gonadotropin from the market. Urinary human menopausal gonadotropin (hMG) preparations were also produced, with subsequent improvements in purification techniques enabling development of products with standardized proportions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity. In 1962 the first reported pregnancy following ovulation stimulation with hMG and ovulation induction with hCG was described, and this product was later established as part of the standard protocol for ART. Improvements in immunopurification techniques enabled the removal of LH from hMG preparations; however, unidentified urinary protein contaminants remained a problem. Subsequently, monoclonal FSH antibodies were used to produce a highly purified FSH preparation containing <0.1 IU of LH activity and <5% unidentified urinary proteins, enabling the formulation of smaller injection volumes that could be administered subcutaneously rather than intramuscularly. Ongoing issues with gonadotropins derived from urine donations, including batch-to-batch variability and a finite donor supply, were overcome by the development of recombinant gonadotropin products. The first recombinant human FSH molecules received marketing approvals in 1995 (follitropin alfa) and 1996 (follitropin beta). These had superior purity and a more homogenous glycosylation pattern compared with urinary or pituitary FSH. Subsequently recombinant versions of LH and hCG have been developed, and biosimilar versions of follitropin alfa have received marketing authorization. More recent developments include a recombinant FSH produced using a human cell line, and a long-acting FSH preparation. These state of the art products are administered subcutaneously via pen injection devices.

Effect of gonadotrophin dose on oocytes yield and quality and embryonic development in Super ovulated mice

Background: Hormonal control for multiple follicular growths in IVF program was directed toward maximizing the yield of fertilizable oocytes, enhance successful implantation and improve early embryonic development. Aim: The effect of different doses of urinary human menopausal gonadotropin (U-hMG) in superovulation regimen was studied. Materials and Methods: Four groups of immature female mouse were sequentially injected by 5 IU, 10 IU, 15 IU and 20 IU of U-hMG followed by injection of 15 IU human chorionic gonadotropin (hCG) for all groups. Mature cumulus oocytes complexes (COCs) were collected 12 hours later then the grading of cumulus cell expansion and oocytes maturity was determined. In vitro fertilization for mature oocytes was done by using epididymal sperm, the embryonic development was followed up till the blastocyst stage. Results: Results demonstrated that the super ovulatory response in immature mice increased with increasing dose of hMG. 15 IU U-hMG was the optimal dose that gave maximum number oocytes with higher maturation rate,minimum degeneration rate and support embryonic development. Conclusion: 15 IU is the optimal dose for induction of superovulation and support in vitro embryo developmentin immature female mice.

Comparison between cycles of the same patients when using recombinant luteinizing hormone + recombinant follicle stimulating hormone (rFSH), human menopausal gonadotropin + rFSH and rFSH only.

IntroductionRecombinant follicle stimulating hormone (rFSH), recombinant luteinizing hormone (rLH), and urinary human menopausal gonadotropin (uHMG) are widely used for controlled ovarian stimulation (COS). This study compares the effects of rFSH only, rLH + rFSH, and HMG + rFSH administration on in vitro fertilization (IVF) outcomes for patients in three different yearly follow-up cycles.Material and methodsThis retrospective, single-center cohort study was conducted from January 2001 to June 2016 at Istanbul Memorial Hospital, Artificial Reproductive Technology Center. From a total of 27,024 IVF cycles in women aged 18 to 45 years (17,536 rFSH only; 2147 rLH + rFSH; 7341 HMG + rFSH), the results of 2,147 cycles receiving a treatment of rLH + rFSH over the 3-year evaluation and 2,081 total cycles in which rLH + rFSH was used at least once were evaluated, and different gonadotropin combinations were compared.ResultsThe age and body mass index of the patients in the uHMG + rFSH group were found to be significantly higher than those of the patients in the rLH + rFSH and rFSH only groups (p < 0.001). The total gonadotropin (GND) dosage of the patients in the rLH + rFSH group was found to be significantly lower than that of the HMG + rFSH group (p = 0.001). No statistically significant differences were found between the clinical and ongoing pregnancy rates, while the highest clinical and ongoing pregnancy rate was observed in the rLH + rFSH group at age 35–39 years.ConclusionsRecombinant luteinizing hormone administration may increase the number of clinical pregnancies for patients aged 35–39 years.

Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.

BackgroundGonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review.MethodsThe review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data.ResultsThe number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones.ConclusionsRecombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.

Gonadotropin-mediated dynamic alterations during bovine oocyte maturation in vitro.

Gonadotropins have been widely used in human-assisted reproduction and animal science for the past four decades. However, the effects of gonadotropins on oocyte maturation at the molecular and biochemical levels are poorly understood. To determine the effects of gonadotropins (recombinant follicle stimulating hormone and urinary human menopausal gonadotropin) on oocyte maturation, we used the bovine oocyte in vitro maturation model. First, we studied the effects of increasing gonadotropin concentrations on nuclear maturation and mitochondrial function in oocytes. Gonadotropins at concentrations of 0.075 and 0.75 IU/ml improved nuclear maturation and increased inner mitochondrial membrane potential and ATP levels; however, there were no beneficial effects at concentrations of 7.5 and 75 IU/ml. Second, we studied the effects of increasing gonadotropin concentrations on the status of methylation in matured (MII) oocytes. Aberrant methylation and demethylation of H19, SNRPN, and PEG3 genes were observed in MII oocytes at all concentrations except 0.075 IU/ml. The expression of genes that function in spindle formation, cell cycle control, and methylation was also downregulated by high gonadotropin concentrations. In conclusion, we established the optimal gonadotropin concentration (i.e., 0.075 IU/ml) to be used for bovine oocyte in vitro maturation studies. These results may provide a guide for clinical stimulation protocols and help to reduce the risks associated with gonadotropin administration during in vitro fertilization treatment.

Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach

BackgroundIatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).Methodology/Principal FindingsUsing a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products.Conclusions/SignificanceThe presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.

Recombinant follitropin alfa/lutropin alfa in fertility treatment

Recombinant human follicle stimulating hormone (rFSH) and luteinizing hormone (LH), also known as follitropin alpha and lutropin alpha, are manufactured by genetic engineering techniques which ensure high quality and batch to batch consistency. Follitropin alpha can be used for controlled ovarian hyperstimulation in assisted reproduction, ovulation induction for WHO group I and II anovulatory infertility and in men with hypogonadotrophic hypogonadism (HH) or idiopathic oligo-asthenospermia. Current evidence suggests superiority of urinary human menopausal gonadotropin (HMG) over follitropin alpha in controlled ovarian hyperstimulation for IVF in terms of live birth rate per couple. Addition of lutropin to follitropin alpha in an unselected IVF population does not appear to confer any benefit; however, it may have a role in ovulation induction in women with hypothalamic hypogonadism. Urinary HMG preparations (especially currently available highly purified preparations) are more cost effective than rFSH in terms of cost per ongoing pregnancy. However, women using rFSH injection pen devices have higher levels of satisfaction as compared to those using urinary HMG by means of conventional syringes.

Long-acting FSH analogue: Corifollitropin-α to sustain multifollicular growth during controlled ovarian stimulation

Different gonadotropin preparations containing FSH are used for ovarian controlled stimulation prior to IVF/intracytoplasmic sperm injection (ICSI). The two most common forms used are urinary human menopausal gonadotropin (containing FSH and LH activity) and recombinant FSH (containing FSH without any LH activity). Owing to the relatively short half-life of all currently used FSH preparations (32 ± 12 h) clinical protocols for induction of multifollicular development in women stimulated for IVF require daily injections. Site-directed mutagenesis and gene transfer techniques were used to develop a longer acting gonadotrophin preparation. Corifollitropin-α (NV Organon, a part of the Schering-Plough Corporation, Oss, The Netherlands) was designed as a sustained follicle stimulant containing the α-subunit of human FSH and a hybrid subunit composed of the sequence of the α-subunit of human FSH and the C-terminal peptide part of the α-subunit of hCG. This molecular structure includes O-linked carbohydrate chain...

Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin

To investigate the differences in the gene expression profile of granulosa cells from preovulatory follicles after controlled ovarian hyperstimulation (COH) with recombinant follicle-stimulating hormone (FSH) or urinary human menopausal gonadotropin (hMG) FSH. Prospective randomized study. University-based facilities for clinical services and research. Thirty women undergoing treatment with vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Patients were randomly allocated to receive recombinant FSH or human (hMG) COH. Granulosa cells were collected from follicular fluid after oocyte retrieval, and mRNA were isolated for gene expression analysis. General gene expression profile. Ninety-six probe sets (85 genes) showed statistically significant differences in expression level in the two groups of granulosa cells. Expression level of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor gene and genes involved in biosynthesis of cholesterol and steroids were expressed at lower levels in the hMG-treated cells; inositol 1,4,5-triphosphate-3-kinase-A and S100-calcium-binding-protein-P (anti-apoptosis protein) were expressed at higher levels in hMG than in recombinant FSH. The different hormone compositions of the two drugs used for COH had a statistically significant impact on the gene expression profile of preovulatory granulosa cells. Some of these genes may be important for periovulatory events, which suggests that the preparation used for COH is important for granulosa cell function and may influence the developmental competence of the oocyte and the function of corpus luteum.

Recombinant-follicle stimulating hormone is more effective than urinary human menopausal gonadotropin in ovarian hyperstimulation for assisted reproductive technology treatment.

Aim: The aim of the present study was to establish a standard protocol for ovarian stimulation with gonadotropin-releasing hormone analog (GnRH-a) long protocol using recombinant-follicle stimulating hormone (rec-FSH) preparations for assisted reproductive technology (ART) treatment. Methods: In 86 patients who underwent ovarian stimulation with GnRH-a long protocol for ART treatment, 53 were stimulated by rec-FSH preparations (rec-FSH group) and the others were stimulated by urinary-hMG (u-hMG group) preparations. The subjects were randomly assigned to either of these preparations. Hormonal profiles, total doses of gonadotropins, duration of stimulation and ART results were compared in both groups. Results: The duration of stimulation was similar in both groups (9.2±0.3days and 9.2±0.2days, respectively). The total doses of gonadotropin in the rec-FSH group (1505.3± 29.2IU) was significantly lower than those in the u-hMG group (2130.3±54.6IU, P<0.0001). The FSH and LH values on the day of human chorionic gonadotropin (hCG) administration in the rec-FSH group were significantly lower than those in the u-hMG group. Pregnancy rates were 31.3% in the rec-FSH group and 33.3% in the u-hMG group, respectively. Conclusions: The present study showed that rec-FSH preparations were more potent than conventional u-hMG preparations and the protocol of the present study with rec-FSH was a new ovarian stimulation protocol with GnRH-a long protocol. (Reprod Med Biol 2007; 6: 27-32).

Use of follicle-stimulating hormone for the treatment of female infertility – current concepts

Ovulatory dysfunction, which is common among women of reproductive age, often results in infertility. Over the last three decades, follicle-stimulating hormone (FSH), in the form of either urinary human menopausal gonadotropin or highly purified urinary FSH (uFSH), has been the mainstay in the treatment of women with ovulatory dysfunction. However, these preparations have several disadvantages, including variable composition, contamination with urinary proteins, and the limited availability of human menopausal urine from which uFSH is extracted. Recombinant human FSH (rhFSH) demonstrates higher purity and specific activity, and is suitable for subcutaneous administration. Additionally, rhFSH has facilitated the development of additional FSH products such as FSH-carboxy terminal peptide that possess different pharmacokinetic and pharmacodynamic properties and may provide more options in the treatment of ovulatory dysfunction and infertility. This article reviews the mechanism of action of FSH in folliculogenesis and ovulation, the current use of FSH in women for the medical management of infertility, and the published clinical experience to date with different rhFSH preparations.

Use of Follicle-Stimulating Hormone for the Treatment of Female Infertility – Current Concepts

Ovulatory dysfunction, which is common among women of reproductive age, often results in infertility. Over the last three decades, follicle-stimulating hormone (FSH), in the form of either urinary human menopausal gonadotropin or highly purified urinary FSH (uFSH), has been the mainstay in the treatment of women with ovulatory dysfunction. However, these preparations have several disadvantages, including variable composition, contamination with urinary proteins, and the limited availability of human menopausal urine from which uFSH is extracted. Recombinant human FSH (rhFSH) demonstrates higher purity and specific activity, and is suitable for subcutaneous administration. Additionally, rhFSH has facilitated the development of additional FSH products such as FSH-carboxy terminal peptide that possess different pharmacokinetic and pharmacodynamic properties and may provide more options in the treatment of ovulatory dysfunction and infertility. This article reviews the mechanism of action of FSH in folliculogenesis and ovulation, the current use of FSH in women for the medical management of infertility, and the published clinical experience to date with different rhFSH preparations.

Menotropins: revisiting the future of controlled ovarian stimulation protocols in assisted reproductive techniques

Objectives: To compare the efficacy & safety of urinary Human Menopausal Gonadotropin (u-hMG; Menodac™; Zydus Biogen, India) versus Recombinant Human Follicle Stimulating Hormone (rec-FSH; Recagon™; Organon, India) for the induction of superovulation in women undergoing Assisted Reproductive Techniques.

The role of gonadotropins in follicular development and their use in ovulation induction protocols for assisted reproduction

During the 1960s, hypogonadotropic patients with polycystic ovary syndrome and those with clomiphene citrate resistance were the first to achieve pregnancy after urinary human menopausal gonadotropin (hMG) administration plus preovulatory human chorionic gonadotropin injection, with cumulative pregnancy rates ranging from 40% to 80% after six to 12 treatment cycles. Ever since, dramatically more progress has been achieved regarding methods and medication in assisted conception techniques, involving both a rapidly increased number of subfertile couples, as well as many practitioners in obstetrics and gynecology. The purpose of this review was to highlight the most crucial historical steps of this remarkable process, by emphasizing the role of gonadotropins in ovulation induction protocols according to the various clinical categories of subfertile patients. In the late 1970s, urinary hMG was the most widely used gonadotropin for ovarian stimulation during in vitro fertilization-embryo transfer for assisted reproduction. The often concurrent problems of premature luteinizing hormone (LH) surges and premature luteinizations, and thus cancellations of the cycles, were efficiently overcome by ‘reversible medical hypophysectomy’, performed by gonadotropin releasing hormone (GnRH) analogs, introduced in 1982. According to its initiation and duration, GnRH analog use was divided into three protocols: the long, most widely used, protocol, which was the best for suppression of endogenous, high tonic LH levels, especially in polycystic ovary syndrome and normogonadotropic patients; and the short and ultra-short protocols, which were mainly used in poor responders to ovarian stimulation treatment, older or hypergonadotropic patients with ovarian failure, because of the well-known ‘flare-up phenomenon’. Recently, GnRH antagonists, which directly do not permit GnRH action by binding to the GnRH gonadotropic cell receptors, have been used, but no final results from large, multicenter clinical trials that are still being undertaken have yet been achieved. Various sub-products of urinary hMG have been produced since the 1980s, with the intention of eliminating most or all of the LH, such as a form with a 3 : 1 proportion ratio between follicle stimulating hormone (FSH) and LH, as well as a form resulting in the removal of almost all of the LH, the ‘pure’ urinary FSH. Finally, in the mid-1990s, recombinant pure FSH was produced in vitro from hamster ovarian cell cultures. The theoretical basis for the broad use of pure urinary FSH and recombinant FSH is that the very low endogenous LH levels after pituitary desensitization are sufficient for proper theca steroidogenesis; still, data in the literature and clinical experience may be controversial upon that issue. From the clinical point of view, clinicians nowadays tend to stimulate polycystic ovary syndrome patients with recombinant FSH plus the application of GnRH analogs in along protocol. However, in poor responders, patients in whom ovulation is resistant to clomiphene citrate, those older than 40 years or hypergonadotropic patients with ovarian failure, urinary hMG, because endogenous LH levels are obviously not sufficient for proper steroidogenesis in the theca cells of the follicles of these patients, is necessary in add to the administration of GnRH analogs in a short or ultra-short protocol. Regarding normogonadotropic women (the majority of patients), most authors agree with the long-protocol application of GnRH analogs. In these patients, it is not certain whether recombinant FSH alone is sufficient for the best possible induction or whether exogenous LH administration in the form of urinary hMG still remains necessary.

Outcome comparison of in vitro fertilization treatment with highly purified subcutaneous follicle-stimulating hormone (Fertinex, a urofollitropin) versus intramuscular menotropins

OBJECTIVE: The aim of this study was to investigate various outcome measures of stimulation with highly purified subcutaneous follicle-stimulating hormone (Fertinex, a urofollitropin) compared with first- and second-generation urinary human menopausal gonadotropin standards (Pergonal, Metrodin). STUDY DESIGN: Retrospective analysis was restricted to our most efficient in vitro fertilization age group (23-34 years). Data from Institute for Assisted Reproduction in vitro fertilization cycles 1 through 11 with Pergonal, Metrodin, or both were tabulated for hormonal values, oocyte quality, and embryo outcome as baseline data. Patients in cycles 12 through 13 were treated with Fertinex and Pergonal or Fertinex alone and then reviewed for the same parameters. RESULTS: Two hundred thirty-eight in vitro fertilization records with embryo transfer were analyzed. Clinical pregnancy rates per embryo transfer in an optimal age group were similar despite use of first- through third-generation urinary gonadotropin preparations: Pergonal and Metrodin, 67%; Metrodin, 64%; Fertinex and Pergonal, 62%; and Fertinex, 54%. There were no discernible differences in hormonal response, oocyte recovery, or embryonic growth. CONCLUSION: Administered subcutaneously, the third-generation urinary gonadotropin preparation Fertinex is effective in in vitro fertilization treatment in young women. (Am J Obstet Gynecol 1998;179:299-307.)