hMG Group Research Articles

A comparison of different therapies for women with polycyatic ovary syndrome

Objective To compare the efficacy and safety of different therapies for sterile women with polycystic ovary syndrome ( PCOS ). Methods 108 sterile women with PCOS who had had medical visits during September 2007 and July 2010 were randomized to CC group, HMG group, CC/HMG group, or LE group, 27 women for each group. Ovulation induction, follicular development, endometrial thickness, and adverse reactions were observed. Results CC group had a higher rate of ovulation but lower rate of pregnancy, thinnest endometrial thickness, and a lower multiple pregnancy rate and OHSS risks. HMG group had higher rates of ovulation and pregnancy, and highest risks of multiple pregnancy and OHSS. LE group had lower rates of ovulation and pregnancy, smallest size of follicles, and lower risks of multiple pregnancy and OHSS. CC/HMG group had higher rates of ovulation, pregnancy, multiple pregnancy, and OHSS risk. Conclusions Four therapies have positive effects on ovulation. HMG and CC plus HMG could result in a higher rate of pregnancy and higher risks of multiple pregnancy and OHSS. LE has a positive effect on the development of follicles and endometrium,but has possible teratogenicity. Key words: HMG; Polycystic ovary syndrome; Infertility; Multiple pregnancy

Effectiveness of highly purified human menopausal gonadotropin in intra-uterine insemination

ObjectiveIn assisted reproductive techniques it is important to find a balance between high pregnancy and acceptable multiple pregnancy rates. In IVF treatment, stimulation with highly purified human menopausal gonadotropin (hMG) results in comparable or even higher pregnancy rates at lower oocyte yields compared to recombinant FSH. Since highly purified hMG contains LH activity, a number of the advantages of highly purified hMG may be attributed to this LH activity. In IUI treatment the effectiveness of highly purified hMG has been barely investigated. The aim of this study was to examine the effectiveness of highly purified hMG in IUI patients treated with a mild stimulation protocol. Study designIn this retrospective study 378 patients were included, receiving 1400IUI cycles between January 2006 and December 2007. Patients were first treated with three subsequent natural cycles without controlled ovarian hyperstimulation, followed by three subsequent cycles stimulated with highly purified hMG. Primary outcomes were ongoing pregnancy rate and multifollicular growth. Secondary outcomes were multiple pregnancy and miscarriage rates. Primary and secondary outcomes were expressed in percentages with associated 95% confidence intervals (95%CI). Differences in the outcomes between natural and stimulated cycles were calculated using χ2 tests. Statistical differences were determined at P<0.05. ResultsOngoing pregnancy rates increased from 6% (95%CI 4.7–7.7) per natural cycle to 7.4% (95%CI 5.2–10.3) per highly purified hMG stimulated cycle (p=0.34). The highest ongoing pregnancy rate was observed in the fifth treatment cycle (10.8% (95%CI 6.6–17)), which is significantly higher than the ongoing pregnancy rate in the unstimulated group (p=0.03). In the highly purified hMG group three (9.7% (95%CI 3.3–24.9)) of the ongoing pregnancies were twin pregnancies, in the unstimulated group there was one (1.7% (95%CI 0.3–9.0)) twin pregnancy (p=0.08). ConclusionOur results indicate that mild stimulation with highly purified hMG in IUI treatment results in an acceptable balance between ongoing and multiple pregnancy rates. Future prospective trials should compare mild stimulation protocols to protocols directly starting with controlled ovarian hyperstimulation. Furthermore, these trials should compare other types and dosages of gonadotropins.

Follicular recruitment is reduced in minimal stimulation for controlled ovarian hyperstimulation using purified human menopausal gonadotropin compared to follicle stimulating hormone

Our hypothesis was that purified human menopausal gonadotropin (hMG) recruits fewer follicles than recombinant follicle stimulating hormone (FSH) in minimal stimulation for controlled ovarian hyperstimulation. A reduction in the number of follicles recruited may translate into a decreased risk of multiple gestation. Retrospective review of minimal stimulation cycles from October 1, 2004 to April 29, 2007. All records from patients having intrauterine insemination (IUI) performed during the time of interest were examined, and data from minimal stimulation cycles were collected. Minimal stimulation consists of 100 mg/d of clomiphene citrate (CC) for cycle days 3–7 followed by a single 150 IU dose of gonadotropins on cycle day 9. The majority of these patients had failed prior CC therapy and were undergoing more aggressive treatment. The choice between using hMG or FSH was generally due to physician preference and was not randomized. We studied midcycle ultrasounds to calculate the number of recruited follicles ≥12 mm. There were 53 patients that contributed to 75 CC/FSH cycles and 28 patients that contributed to 35 CC/hMG cycles. The hMG and FSH groups were similar with respect to: age (35.3 vs. 35.3, P=0.9); day 3 FSH (8.8 vs. 7.9, P=0.3); antral follicle count (AFC) (12.1 vs. 12.5, P=0.8); body mass index (BMI) (25.5 vs. 25.0, P=0.7); diagnosis (P=0.9); and the cycle day on which the ultrasound was performed (12.0 vs. 11.6, P=0.07). The hMG group recruited significantly fewer follicles than the FSH group. The endometrial thickness and pregnancy rates were similar for the 2 groups. There were no multiple gestations in the hMG group, while 3 of the 10 pregnancies in the FSH group were twins. TableCycle Outcome DataCC/hMGCC/FSHP value# of follicles ≥12 mm2.71 (2.22, 3.20)3.39 (3.02, 3.75)P<0.05Endometrial thickness (mm)7.77 (7.23, 8.31)8.11 (7.54, 8.67)P=0.4Pregnancy rate (%)14.3 (2.3, 28.9)13.9 (5.6, 21.8)P=0.9Data presented are means (95% CI). Open table in a new tab Data presented are means (95% CI). Multivariate analysis controlling for age, day 3 FSH, AFC, BMI, diagnosis, and cycle day on which the ultrasound was performed confirmed a significant decrease in the number of follicles recruited in the hMG group (P<0.05). Minimal stimulation with hMG was associated with a 20% reduction in the number of follicles recruited compared to FSH. This reduction appears to reduce the risk of multiple gestation without reducing the pregnancy rate.

Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study

A comparison of the effectiveness of different gonadotrophin preparations in intrauterine insemination (IUI) cycles for patients with unexplained infertility was performed. Two hundred and forty-one patients were prospectively randomized using computer-generated random numbers into three groups: 81 in the Follitropin alpha (Group I), 80 in the urinary FSH (uFSH) (Group II) and 80 in the hMG (Group III). The primary outcome was clinical pregnancy rate with duration of stimulation, total gonadotrophin dose, number of dominant follicles, clinical pregnancy rate, multiple pregnancy, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate being secondary outcomes. Clinical pregnancy rate was significantly higher in the rFSH group (25.9% in Follitropin alpha, 13.8% in uFSH and 12.5% in HMG groups; P = 0.04). There was no significant difference in terms of duration of stimulation, but mean FSH dose consumed per cycle was significantly lower in the recombinant FSH (rFSH) group compared with others (825 IU in Follitropin alpha, 1107 IU in uFSH and 1197 IU in HMG groups; P = 0.001). The number of follicles > or =16 mm diameter was significantly higher in the rFSH group compared with the uFSH and HMG groups (2.6 in Follitropin alpha, 1.3 in uFSH and 1.4 in HMG groups; P = 0.001). rFSH may result in a better outcome in IUI cycles for unexplained infertility.

P-87: Comparative profile of ART patients treated with hMG or recombinant FSH. French experience

Since several years, recombinant FSH (r-FSH) have been replacing urinary products in controlled ovarian hyperstimulation (COH), particularly in ART, because of hypothezised advantages on safety and efficacy, which resulted in a large increase of cycles cost. However, several recent meta-analyses were unable to find any difference in terms of pregnancy rate (PR), and no specific safety risk was ever demonstrated for urinary products. Moreover, the beneficial role of LH activity has been analyzed in many studies, leading to use more widely hMG. In this debate, it was useful to better understand the reasons related to the medical choice of one type of drug or the other. French multicenter study carried in 20 voluntary centers. Retrospective analysis of clinical data routinely collected in their medical files in 2003 and 2004 . 20 centers were recruited on the following criteria: routine use of hMG (more than 10% of the cycles), willingness to participate, existence of computerized routine data on IVF. A form was designed, including the patients’ age, the infertility characteristics (infertility duration, past history of pregnancy, ovulation quality, tubal status, endometriosis, semen characteristics), the main cycle characteristics (down regulation, controlled ovarian hyperstimulation) oocyte recovery, laboratory results and cycle outcome. Two groups were constituted, one with cycles treated with hMG, and the second with r-FSH. At this step, patients receiving both types of drugs or with spontaneous cycles were excluded. Those two groups were compared on all the patients’ characteristics, to analyze the factors implicated in the medical choice, but not on the efficacy results, since the hypothesis was that patients were not similar and the drug administration was not randomized. The statistical analysis was done using the SAS software, with tests adapted to the studied variables nature, and a p value at 0.05 for significance. The final population of the study was composed of 15,000 cycles, of which 24% received hMG. Women treated with hMG represented 27.5% of IVF cycles and 22.1% of ICSI cycles. The group receiving hMG was constituted of women older than the other (35.7 [SD=4.4] vs. 34.2 [4.5], p<0.001). There were more women aged more than 35 years (60.4 % vs. 45.4%, p<0.001), and aged more than 40 (22.9% vs. 13.3%, p<0.001). Men were also older, even if the difference was smaller (37.0 [5.8] vs. 36.3 [5.8], p<0.01). There was no difference in infertility duration (5.6 [2.7] in hMG group vs. 6.5 [3.1], p=0.59). The number of previous ART cycles was higher in the hMG group (1.3 [1.5] vs 1.0 [1.3]. In conventional IVF, there were more blocked tubes (42.7% vs. 36.4%, p<0.01), more endometriosis (7.2% vs. 5.0%, p=0.02). The percentage of male infertility and of unexplained infertility were similar (respectively 44.9% vs. 45.8%, p=0.64 and 14.0% vs. 11.6%, p=0.09). In patients treated by ICSI, those without male infertility were more frequent in the r-FSH group (19.8% vs. 12.1%, p<0.001). Clearly, the patients’ characteristics have an influence on the medical choice of the drug used for COH. This must be carefully taken in account when comparing the results of those products in non randomized observational studies.

Controlled ovarian stimulation with exclusive FSH followed by stimulation with hCG alone, FSH alone or hMG

Objective To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase. Study design In a prospective randomized controlled trial, 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG (200 IU/day) (hCG group, n = 17), hMG (225 IU/day) (hMG group, n = 17) or rFSH (200 IU/day) (FSH group, n = 17) in the late stage of follicular development. Parameters of follicular response and serum estradiol, progesterone and testosterone levels were assessed. Results Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups. Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group. Clinical pregnancy rates were similar for all groups. The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH. Conclusions LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH, even though the patients showed higher serum progesterone levels on the hCG day.

Lutropin Alpha in Controlled Ovarian Hyperstimulation for In Vitro Fertilization: A Retrospective Analysis

To analyse the effect of recombinant LH used from the beginning of controlled ovarian hyperstimulation (COH) in patients of all ages undergoing in vitro fertilization (IVF). A single private IVF centre retrospective cohort analysis. The analysis included 300 consecutive ART cycles stimulated with follitropin alpha and menotropin (n=137) or with follitropin alpha and lutropin alpha (n=163), from July 2003 to March 2005. Assignment of patients to either group was based on patient choice and depended on cost. Patients stimulated with menotropin only were excluded from this analysis. A downregulation (n=181) or a microflare protocol (n=99) was used. Depending on patient characteristics, the starting dose of follitropin alpha varied from 150 to 450 IU/day and was associated with 75 to 150 IU of lutropin alpha or 1 to 4 ampoules of menotropin. Final follicular maturation was triggered with 10.000 IU of human chorionic gonadotropin 36 hour prior to egg retrieval and the luteal phase was supported with progesterone. Patients were grouped by the administration of lutropin alpha or menotropin. Factors for stratified analyses were age ≤ 35 or > 35 years and type of protocol. Overall, patients in the lutropin alpha group were 1.2 years younger than those in the HMG group; there was no significant difference in stimulation days, number of embryos transferred and cumulative mean number of FSH 75 IU equivalents used to complete COH. The cumulative mean number of LH 75 IU equivalents used was significantly lower in the lutropin alpha than in the menotropin group. Although not reaching statistical significance, the pregnancy rate was higher in the lutropin alpha group (Table 1). When the different subgroups were analysed, in all cases the number of LH 75 IU equivalents used was significantly lower in the lutropin alpha than in the menotropin group and pregnancy rates were comparable. Patients > 35 years stimulated with a downregulation protocol (Table 2) needed 2.6 times less LH equivalents when supplemented with lutropin alpha than with menotropin and showed the greatest benefit from the use of lutropin alpha over HMG Tabled 1 The results of this retrospective analysis suggest that lutropin alpha can be used efficiently for LH supplementation in COH from day 1 of ovarian stimulation. Prospective studies are needed to confirm these findings.

Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin

Objective. This study evaluated the psychological side-effects of clomiphene citrate (CC) and hMG in women undergoing fertility treatment.Method. This study was a cross-sectional, self-report survey of 454 women at various stages of treatment for infertility. At the time of study, 139 women had not taken fertility drugs and 315 women had taken one or more cycles of CC or hMG. All subjects were asked to complete the State-Trait Anxiety Inventory (STAI). Women taking CC or hMG were also asked to complete a self-administered questionnaire on the side-effects of their medications.Result(s). In the CC group (n = 162) and hMG group (n = 153), 77.8% (126 of 162) and 94.8% (145 of 153) reported at least one side-effect, respectively. Irritability, mood swings, feeling down, and bloating had high frequencies in both CC and hMG groups, with a higher mean number of side effects reported in the hMG group (4.4 ± 3.7 for the CC group and 6.8 ± 3.7 for the hMG group, p < 0.001). There was no significant difference among the CC, hMG and no medication groups for mean state and trait anxiety scores. However, there were significant differences among the three side-effect groups (those who reported 1 to 4, 5 to 7, and more than 7 side-effects) for the mean scores of state (df = 2, F = 8.7, p < 0.001) and trait (df = 2, F = 11.9, p < 0.001) anxiety in women taking fertility drugs.Conclusion(s). Women taking CC or hMG reported high frequencies of psychological side-effects, and should be advised of these before treatment.

The effect of HMG and recombinant human FSH on oocyte quality: a randomized single-blind clinical trial

Objective: To compare the effect of HMG and rhFSH on oocyte quality in ICSI cycle. Setting: Vali-e-Asr university teaching hospital. Method: Prospective single-blind randomized clinical trial. Subjects: Sixty women undergoing ovarian stimulation for ICSI were randomized to receive a standard protocol of either HMG or rhFSH in down-regulation cycles. Interventions: Prior to microinjection, each oocyte was assessed regarding the nuclear maturity, morphology of zona plucida, cytoplasmic appearance and polar body morphology. Fertilization rate was followed. Main outcome: The percentage of metaphase II oocytes in HMG and rhFSH groups. Statistical analysis: Statistical analyses were carried out by the Mann–Whitney, Fisher's exact, χ 2 tests and Student's t-test. Results: No significant differences were found between two groups in regard to the demographic data, the ovarian response and pregnancy/implantation rates ( P > 0.05). The percentage of metaphase II oocytes in HMG and rhFSH groups were 81.3% versus 80.6%, respectively. Conclusions: There were no significant differences between parameters such as, oocyte quality and percentage of metaphase II oocytes between these two groups.

Comparação entre três esquemas de indução da ovulação para inseminação intra-uterina com relação à espessura endometrial e taxa de gravidez

PURPOSE: to compare pregnancy rates and mean endometrial thickness obtained with three protocols for induction of ovulation in cycles of intrauterine insemination (IUI). METHODS: one hundred and ten IUI cycles were retrospectively evaluated in the study, divided into three groups, according to the used ovulation induction protocols: 100 mg clomiphene citrate (CC) on days 3 to 7 of the cycle (CC group, n=24), 100 mg/day CC on days 3 to 7 of the cycle + 75 IU/day of human menopausal gonadotrophin (hMG) on days 3, 5 and 7 of the cycle (CC+hMG group, n=29), and 75 IU/day of hMG on days 3 to 8 of the cycle (hMG group, n=57). Statistical analysis was performed using Student's t test to compare the means and the c2 test to compare the rates. Results were considered statistically significant at p<0.05. RESULTS: the patients' average age at the onset of the first cycle was 2340 years (mean age, 33.3 years). There were no statistically significant differences between groups. The mean endometrial thickness on the day of the human chorionic gonadotrophin (hCG) administration was significantly higher in the hMG group (10.2±0.2 mm), as compared with the CC and CC+hMG group (7.9±0.4 and 8.7±0.2 mm, respectively, p<0.001). The overall clinical pregnancy rate was 18.2%, and there were no statistically significant differences between the groups (CC group=12.5%; CC+hMG group=24.1% and hMG group=19.3%). CONCLUSION: the results indicate higher mean endometrial thickness in the hMG group as compared with the CC group and the CC+hMG group. There were no significant differences between clinical pregnancy rates obtained with each protocol (CC, CC+hMG and hMG).

LH as a low dose chorionic gonadotropin for late stage ovulation induction: comparison with human menopausal gonadotropin

The aim of this prospective study is to assess if LH in the form of a human chorionic gonadotropin (hCG) low dose is similar to human menopausal gonadotropin (hMG) in late stage of ovulation induction, measured based on the number of small ovarian follicles and the chance of premature follicle luteinization. Methods: Thirty-four normovulatory women undergoing an ICSI cycle treatment were randomly assigned to two treatment groups (17 each). Both GnRH agonist-suppressed groups received recombinant (rFSH) (200 IU/day) until the dominant follicle(s) were 13–14 mm followed by hCG (200 IU/day) (hCG group) or hMG (225 IU/day) (hMG group) until parameters for pre-ovulatory hCG administration were reached. Monitoring included transvaginal ultrasound and estradiol, progesterone and testosterone measurements. Results: Small pre-ovulatory ovarian follicle occurrence and the ovarian stimulation number of days were similar in both groups. Fourteen out of 17 patients in the hCG group had a serum progesterone level >1.5 ng/ml on the pre-ovulatory hCG day, compared to six patients in the hMG group. Clinical pregnancy rates were similar in hCG and hMG groups (52.9% and 33.3%, respectively). Total cost of the hCG group treatment was significantly lower than control group's (R$ 2363.00±409.70 vs. R$ 1949.00±292.40, respectively; p=0.0019). Conclusions: LH in the form of a hCG low dose at the late follicular phase induced the same follicular pattern as hMG after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG, even showing higher serum progesterone levels on the pre-ovulatory hCG day.

Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study

We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization – embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the Δ-5 steroid synthesis pathway in the adrenals and/or in the ovary.

Follitropin-α versus human menopausal gonadotropin in an in vitro fertilization program

Objective To compare the efficacy of recombinant FSH and urinary-derived hMG for ovarian stimulation during IVF. Design Retrospective analysis of data from IVF cycles conducted over 15 months. Setting University hospital IVF unit. Patient(s) Three hundred twenty-four women undergoing their first to sixth IVF cycle. Intervention(s) After pituitary down-regulation, patients received recombinant FSH or hMG, according to personal choice. After hCG administration, patients underwent oocyte retrieval, oocyte fertilization, and embryo transfer. Main outcome measure(s) Implantation rate and clinical ongoing pregnancy rate per oocyte retrieval. Result(s) Patients who chose recombinant FSH were slightly younger than those who chose hMG (34.1 vs. 35.1 years, respectively). Although more embryos were transferred in the hMG group (3.6 vs. 3.2), the ongoing pregnancy and implantation rates were significantly higher in the recombinant FSH group (ongoing pregnancy rate, 50.0% vs. 36.2%). Conclusion(s) Recombinant FSH is more effective than hMG for ovarian stimulation in IVF cycles. This increased efficacy, which is achieved with fewer ampoules, is likely to offset the higher acquisition costs of recombinant FSH.

Role of intracellular cyclic adenosine 3',5'-monophosphate concentration and oocyte-cumulus cells communications on the acquisition of the developmental competence during in vitro maturation of bovine oocyte.

The present study was designed to address the physiological role played by cAMP on gap junction (GJ) mediated communications between oocyte and cumulus cells during in vitro maturation. Cyclic AMP was stimulated by different collection and maturation media known to induce different rates of nuclear maturation and developmental competence as well as different levels of cumulus expansion. Cumulus-oocyte complexes (COCs) were matured for 0, 3, 7, 12, 18, and 24 h in the absence of stimulation or in the presence of serum and gonadotropins (fetal bovine serum+human menopausal gonadotropins [FCS+hMG]) or 0.01 microg/ml of invasive adenylate cyclase (iAC). For each time point, intracellular cAMP concentration ([cAMP]i) was determined either in the whole COC or oocyte after cumulus cell removal. GJ functional status was analyzed by microinjection of Lucifer yellow fluorescent dye in cumulus-enclosed oocytes and by immunohistochemical localization of connexin 43 (Cx43). In the absence of stimulation, [cAMP]i in COC and oocyte was lower than in other groups, and communications declined after 3 h of culture. In the FCS+hMG group, [cAMP]i increased significantly in COC, with a peak between 3 and 7 h that was temporally correlated with the beginning of the cumulus expansion process, which occurred only in this group and with the termination of the communications. COC matured in the presence of iAC showed a moderate increase of [cAMP]i during all of the maturation times as well as a prolongation of oocyte-cumulus cell communications. The immunohistochemical localization of Cx43 confirmed the delay in connexons protein turnover in iAC-treated COCs. Our results show that cumulus expansion and oocyte developmental competence are induced by different levels of cAMP and that its intracellular concentration may affect cell coupling between oocyte and cumulus cells. We hypothesize that the higher developmental competence of COCs matured in the presence of iAC could be achieved through a moderate increase of intracellular cAMP, which in turn determines a prolongation of communications between the two cell types.

A pharmacokinetic and endocrine comparison of recombinant follicle-stimulating hormone and human menopausal gonadotrophin in polycystic ovary syndrome

Elevated LH concentrations are frequently encountered in patients with polycystic ovary syndrome (PCOS) and increased LH (either endogenous or superimposed through the use of HMG) may have detrimental effects on reproductive function. In spite of this, FSH-only products and HMG have been used indiscriminately for ovulation induction – on the basis that the administration of HMG to patients with PCOS, who are not receiving GnRH agonists, does not result in significant increases in serum LH concentrations as judged by daily single blood samples. However, both endogenous and exogenous LH have a relatively short terminal half-life and studies have reported normal serum LH, but abnormal urinary LH and emphasized that early morning urinary measurements are more informative than those in serum because they reflect nocturnal LH secretion. Therefore, the present study was undertaken to perform a pharmacokinetic and endocrine comparison of recombinant human FSH and HMG in PCOS patients including LH measurements in the urine. Five PCOS patients receiving s.c. recombinant human FSH (rhFSH) and five PCOS patients receiving i.m. HMG for ovulation induction according to a chronic low-dose step-up regimen underwent blood and urine sampling at the following study points: Point 0 was the day of HCG injection; Points 1 to 5 corresponded to days HCG −1 to −2; −3 to −4; −5 to −6; −7 to −8; and −9 to −10; respectively. Serum hormone measurements included oestradiol, FSH, LH, progesterone, inhibin A, androstenedione, testosterone, and free testosterone index. FSH and LH were also measured daily in 8-h urine samples reflecting overnight renal urine secretion. Hormone concentrations calculated as the area under the curve showed that both FSH and LH concentrations in urine were significantly higher in HMG group than in group rhFSH. It is concluded that both LH and FSH concentrations significantly accumulate in the urine of PCOS patients receiving HMG for ovulation induction in a chronic low-dose protocol as compared with rhFSH treatment.

Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome

Objective: To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. Design: Parallel group design. Prospective, randomized clinical study. Setting: A tertiary care infertility clinic. Patient(s): A total of 578 patients of our IVF/ICSI routine were recruited. Intervention(s): Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively. Main Outcome Measure(s): Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality. Result(s): Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant ( P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality. Conclusion(s): In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated.

Two distinct subgroups of Group B Sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken

Group B Sox genes, Sox1, -2 and -3 are known to activate crystallin genes and to be involved in differentiation of lens and neural tissues. Screening of chicken genomic sequences for more Group B Sox genes identified two additional genes, Sox14 and Sox21. Proteins encoded by Sox14 and Sox21 genes are similar to each other but distinct from those coded by Sox1-3 (subgroup B1) except for the HMG domain and Group B homology immediately C-proximal of the HMG domain. C-terminal domains of SOX21 and SOX14 proteins function as strong and weak repression domains, respectively, when linked to the GAL4 DNA binding domain. These SOX proteins strongly (SOX21) or moderately (SOX14) inhibited activation of δ 1-crystallin DC5 enhancer by SOX1 or SOX2, establishing that Sox14 and Sox21 are repressing subgroup (B2) of Group B Sox genes. This provides the first evidence for the occurrence of repressor SOX proteins. Activating (B1) and repressing (B2) subgroups of Group B Sox genes display interesting overlaps of expression domains in developing tissues (e.g. optic tectum, spinal cord, inner ear, alimentary tract, branchial arches). Within each subgroup, most expression domains of Sox1 and -3 are included in those of Sox2 (e.g. CNS, PNS, inner ear), while co-expression of Sox14 and Sox21 occurs in highly restricted sites of the CNS, with the likely temporal order of Sox21 preceding Sox14 (e.g. interneurons of the spinal cord). These expression patterns suggest that target genes of Group B SOX proteins are finely regulated by the counterbalance of activating and repressing SOX proteins.

The effects of epidermal growth factor and insulin-like growth factor I on the metabolic activity, nuclear maturation and subsequent development of cattle oocytes in vitro.

The effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the maturation and subsequent development of cattle oocytes in vitro were evaluated in three experiments. Cumulus-oocyte complexes (COC) were collected from cattle ovaries and matured for 20-24 in control medium or in medium containing 50 ng EGF ml-1, 100 ng IGF-I ml-1, EGF + IGF-I, or 10% (v/V) fetal calf serum plus 0.1 i.u. human menopausal gonadotrophin ml-1 (hMG). In Expt 1, treatment with EGF + IGF-I stimulated cumulus expansion, the metabolism of pyruvate and glutamine, and nuclear maturation. In Expt 2, only the metabolic measurements from oocytes that reached metaphase II were considered, and EGF + IGF-I stimulated pyruvate metabolism to the same extent as serum + hMG. In Expt 3, the oocytes were fertilized after maturation culture, and the resultant embryos cultured for up to 8 days. The cleavage was greater in the EGF and EGF + IGF-I groups than in the controls but less than in the serum + hMG group. Moreover, the number of blastocyst cells at 7 days after insemination and the proportion of cleaved embryos that developed to the blastocyst stage by day 8 was greater in the serum + hMG group than in the control group indicating that maturation treatment can affect early embryonic development. In conclusion, EGF + IGF-I can stimulate cumulus expansion, oxidative metabolism, nuclear maturation and cleavage after fertilization of bovine oocytes in vitro. The relative effects of the treatments on oocyte pyruvate metabolism in Expts 1 and 2 generally paralleled their effects on cleavage and subsequent development in Expt 3, suggesting that mitochondrial function is related to developmental potential. Further investigation is required to determine which component(s) of serum or gonadotrophin treatment is responsible for the effects on subsequent embryonic development.

Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone

To compare the in vitro fertilization and embryo transfer (IVF-ET) outcome of a 3-day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. The IVF-ET program. Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. The ultrashort protocol, although being convenient and having some advantages found in the long GnRH-a protocol, is inferior in its outcome compared with the two other protocols.

Gonadotropins and combined gonadotropin-releasing hormone agonist-gonadotropins protocols in a randomized prospective study

A prospective study was designed to compare cycles stimulated by human menopausal gonadotropin (hMG) (group A) with cycles pretreated with gonadotropin-releasing hormone agonist causing pituitary desensitization followed by hMG stimulation (group B). Three hundred two cycles were randomly allocated to each group. Cancellation rate was 27.2% in group A compared with only 3.3% in group B. Significantly less hMG ampules for a shorter period were needed in group A patients. Lower estradiol and higher luteinizing hormone levels were detected in the hMG group. Patients in group B yielded significantly more oocytes and more embryos per retrieval. A significantly higher pregnancy rate per cycle was obtained in group B (27%) as compared with that of group A (13%). Moderate and severe ovarian hyperstimulation syndrome was significantly more frequent in group B than in group A.