Dose Of Recombinant Follicle Stimulating Hormone Research Articles

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection

To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). Prospective study. University. One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval.

Physical symptoms throughout IVF cycles

The physical impact of in vitro fertilisation (IVF) is not well explored. The aim of this prospective controlled longitudinal study was to examine the impact of 11 symptoms during an entire long down regulation (LDR) cycle and to determine the effect of the mean recombinant follicle stimulating hormone (RecFSH) dose and ovarian responsiveness of patients and outcome had on reported symptoms. The severity of symptoms was measured using a daily questionnaire to determine a total summary score (TSS) for each symptom, a summary symptom score (SSS) based on all TSS and a mean daily severity for each symptom. Outcome was determined by beta human chorionic gonadotroophin (β-hCG) test result. 79.1% of women undertaking LDR IVF cycles had significant physical symptoms. Treatment symptom severity peaked at oocyte retrieval, with prominent symptoms including bloating, abdominal pain/cramps and fatigue. No relationship was found between outcome, RecFSH dose and ovarian responsiveness with reported symptoms. In conclusion, IVF places a real physical burden on women should be encouraged to reduce undertaking LDR cycles. The impact of the symptoms, particularly the increase in severity leading up to day of oocyte retrieval suggests that women may be warned to reduce stress and activities during this time.

Clinical outcomes in relation to the daily dose of recombinant follicle-stimulating hormone for ovarian stimulation in in vitro fertilization in presumed normal responders younger than 39 years: a meta-analysis

The optimal ovarian stimulation dose to obtain the best balance between the probability of pregnancy and the risk of complications, while maximizing cost-effectiveness of in vitro fertilization (IVF) treatment, is yet to be established. A systematic search of the electronic databases PubMed, EMBASE and Cochrane library, from 1984 until October 2009 for randomized controlled trials comparing different doses of recombinant FSH in IVF, was performed. Ten studies (totaling 1952 IVF cycles) were included in the present meta-analysis, comprising patients younger than 39 years with regular menstrual cycle, normal basal FSH levels and two normal ovaries. Comparison was made between studies using a daily dose of 100 versus 200 IU recFSH, and between 150 versus 200 IU recFSH or higher. Although oocyte yield was greater in the >200 IU/day dose group, pregnancy rates were similar compared with lower dose groups. The risk of insufficient response to ovarian stimulation was greatest in the 100 IU/day dose group. The risk of developing ovarian hyperstimulation syndrome was greater in the >200 IU/day dose group. The number of embryos available for cryopreservation was lowest in the 100 IU/day group, but similar comparing the 150 IU/day and the >200 IU/day dose groups. This meta-analysis suggests that the optimal daily recFSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy and embryo cryopreservation rates. Furthermore, the wide spread adherence to this optimal dose will allow for a considerable reduction in IVF costs and complications.

Extensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates

Study Objective We sought to compare the outcomes of in vitro fertilization (IVF) treatments in women with infertility-associated deep infiltrative endometriosis (DIE) who underwent extensive laparoscopic excision of endometriosis before IVF with those who underwent IVF only. Design Prospective cohort study. Setting Infertility clinic and private hospital in São Paulo, Brazil. Patients A total of 179 infertile patients younger than 38 years had symptoms and/or signs of endometriosis and sonographic images suggestive of DIE. Interventions After thorough counseling, 179 women were invited to participate in a prospective cohort study with 2 treatment options: IVF without undergoing laparoscopic surgery (group A, n = 105) and extensive laparoscopic excision of DIE before IVF (group B, n = 64). Ten women were lost to follow-up. The IVF outcomes were compared between the 2 groups. Measurements and Main Results In group B, patients had 5 ± 2 (mean ± SD) DIE lesions excised during laparoscopy. Patient characteristics in groups A and B, respectively, were: age (32 ± 3 vs 32 ± 3 years, p = .94), infertility duration (29 ± 20 vs 27 ± 17 months, p = .45), day-3 serum follicle-stimulating hormone levels (5.6 ± 2.5 vs 5.9 ± 2.5 IU/L, p = .50), and previous IVF attempts (1 ± 1 vs 2 ± 1, p = .01). The IVF outcomes differed between groups A and B, respectively, with regard to total dose of recombinant follicle-stimulating hormone required to accomplish ovulation induction (2380 ± 911 vs 2542 ± 1012 IU, p = .01), number of oocytes retrieved (10 ± 5 vs 9 ± 5, p = .04), and pregnancy rates (24% vs 41%, p = .004), but not number of embryos transferred (3 ± 1 vs 3 ± 1, p = 1). The odds ratio of achieving a pregnancy were 2.45 times greater in group B than in group A. Conclusion Extensive laparoscopic excision of DIE significantly improved IVF pregnancy rates of women with infertility-associated DIE.

Ovarian Stimulation in Obese and Non-Obese Polycystic Ovary Syndrome Using a Low-Dose Step-Up Regimen with Two Different Starting Doses of Recombinant Follicle-Stimulating Hormone

Sixty-seven infertile women with polycystic ovary syndrome (PCOS) were divided into two groups, obese and non-obese, according to their body mass index. Waist-to-hip ratio, insulin resistance, total testosterone and dehydroepiandrosterone sulphate levels were significantly elevated in obese, compared with non-obese, patients. Both groups were treated with a low-dose step-up protocol of recombinant follicle-stimulating hormone (rFSH) with a starting dose of 50 IU/day and, every third day, a 25-IU increase in the dose until the appropriate dose was achieved for each individual, up to a maximum of 175 IU/day. In the obese group only, repeat therapy commenced in the second ovulatory cycle in women who had not become pregnant, however a starting dose of 75 IU/day was then used, with incremental and maximum dose as before. The results of the starting dose of 75 IU/day rFSH were compared with the results of a 50 IU/day rFSH starting dose in the obese group. A starting dose of 50 IU/day rFSH in a low-dose step-up regimen was found to be effective, safe and well-tolerated for inducing follicular development in non-obese infertile women with PCOS. However, for obese PCOS patients, a starting dose of 75 IU/day rFSH is recommended.

Fixed-dose of recombinant follicle stimulating hormone (200 IU vs 300 IU) in indian women undergoing intracytoplasmic sperm injection: a comparative study

OBJECTIVE: There are few studies in Indian populations with different doses of recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation (COS). Hence, this study was planned to compare the efficacy of two (fixed) doses of rFSH in COS protocol. DESIGN: An open label, prospective, randomized study comparing the effect of 200 IU or 300 IU daily fixed-dose of rFSH in women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: 59 female subjects (aged between 25-30 years), undergoing 1st cycle for treatment of male factor infertility, with normal cycles (mean length between 24 and 35 days) and body mass index of 18 to <30 kg/m2 were enrolled. Eligible subjects following down regulation with Lupride from day 21, received either 200 IU or 300 IU of daily dose of rFSH (Recagon; Organon) starting from 2nd/3rd day of the period according to the randomization. On the 6th day of stimulation, 150 IU of Human Menopausal Gonadotropin (hMG) (Menopur; Ferring) was added if there were <5 follicles of 10 mm in both ovaries combined. Human chorionic gonadotropin (hCG) was administered with >4 follicles of ≥18 mm diameter and endometrial thickness of >8 mm. Ovum pick-up was done 35 hours after hCG injection followed by luteal support with progesterone. The primary end points were number of cumulus-oocyte complexes, total dose of rFSH used, ongoing clinical pregnancy and implantation rates. Secondary end points were treatment length, the number of follicles (on the day of hCG administration), mature oocytes, good quality embryos, percentage of patients requiring hMG, incidence of ovarian hyperstimulation syndrome (OHSS), cancellation and clinical pregnancy rate. RESULTS: A total of 59 women were treated with 200 IU (n=28) and 300 IU (n=31) of rFSH. In comparison to 300 IU, the 200 IU treated group had a higher number of cumulus-oocyte complexes retrieved (16.0 vs 10.9; p<0.01), lesser rFSH used (2014 vs 3029 IU; p<0.001), comparable implantation rate (19.7% vs 8.6%; NS) and comparable ongoing clinical pregnancy rates per started cycle (32.1% vs 16.1%; NS). A significantly higher number of matured oocytes (14.2 vs 9.2, P<0.01) and good quality embryos (8.6 vs 5.5; P<0.01) were retrieved in 200 IU group as compared to 300 IU group. CONCLUSIONS: Current study suggests that the use of a lower dose (200 IU) instead of a higher dose (300 IU) of rFSH, in Indian infertile women, may offer equivalent benefits.

Effect of letrozole at 2.5 mg or 5.0 mg/day on ovarian stimulation with gonadotropins in women undergoing intrauterine insemination

To determine the effect of combined therapy of letrozole (2.5 mg or 5.0 mg) with recombinant follicle-stimulating hormone (FSH) in comparison with the administration of recombinant FSH alone in an intrauterine insemination (IUI) program. Retrospective study. Assisted fertilization program in a specialized infertility center. 110 women undergoing IUI and gonadotropin therapy. Recombinant FSH alone administered from day 3 or combined with letrozole, 2.5 or 5.0 mg/day, on days 3 to 7, and gonadotropins starting on day 7 of the menstrual cycle. Transvaginal ultrasound examinations were done until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of human chorionic gonadotropin (hCG), and IUI performed 30 to 40 hours later. Recombinant FSH dose required, number of follicles greater than 14 mm and 18 mm, endometrial thickness, pregnancy rates, miscarriages, and characteristics of newborns. Women treated with FSH and 5.0 mg/day of letrozole required a lower dose of FSH than the group cotreated with 2.5 mg/day of letrozole or with FSH alone. Throughout most of the follicular phase, the endometrial thickness was statistically significantly less in both letrozole cotreatment groups compared with the FSH control group. By the day of hCG administration, the endometrial thickness was comparable among all the groups. The pregnancy rates were the same with recombinant FSH alone or combined with letrozole. In terms of cost-effectiveness, 5.0 mg/day of letrozole is more effective than the 2.5 mg/day in cotreatment with no adverse effect on pregnancy rate or outcome.

Clinical efficacy of the gonadotropin‐releasing hormone antagonist, ganirelix, in Korean women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer with recombinant follicle‐stimulating hormone

To assess the clinical efficacy and safety of the gonadotropin-releasing hormone (GnRH) antagonist, ganirelix (Orgalutran), treatment in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. This was a non-comparative, open-label, single-center trial carried out on 31 infertile Korean women. A daily dose of 0.25 mg of the GnRH antagonist, ganirelix, was given, beginning on the sixth day of recombinant follicle-stimulating hormone (FSH) treatment. If the ovarian response was low, ganirelix treatment was delayed until the leading follicle reached a mean diameter of 14 mm. The ganirelix treatment was continued until the day of human chorionic gonadotropin (hCG) injection. Descriptive statistics were recorded for all parameters. The median duration of ganirelix treatment was 4 days (range: 2-6 days) and the median total recombinant FSH dose was 1350 IU (900-2350 IU). During ganirelix treatment, the incidence of luteinizing hormone (LH) rises (LH = 10 IU/L) was 3.2% (one of 31 cases). On the day ovulation was triggered by hCG, the mean number of follicles >/=11 mm in diameter was 12.4 +/- 4.5, and the median of serum estradiol concentration was 4289.9 (1893.7-8268.5) pmol/L. The mean number of oocytes per retrieval was 10.9 +/- 6.1. The fertilization rate was 61.5%, and the mean number of replaced embryos was 2.8 +/- 0.6. The mean implantation rate was 10.0%, and the clinical pregnancy rate per transfer was 23.3% (seven of 30 cases) and the ongoing pregnancy rate per transfer was 20.0% (six of 30 cases). The results of the present study support ganirelix as a safe, short, convenient and effective treatment for patients undergoing COH for IVF in Korean women.

Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long‐standing hypogonadotrophic hypogonadism

A 31 year old patient with primary amenorrhea, primary infertility and long-standing hypogonadotrophic hypogonadism presented to our infertility unit in June 2003. Immediately prior to her referral to our clinic, the patient was on sequential hormone replacement therapy for one year in view of moderate lumbar spine osteopenia detected on DEXA bone densitometry, which she discontinued because she wished to conceive. In the past, the patient used oral contraceptive pills to induce regular withdrawal bleeding. A routine series of infertility investigations was performed. Hormonal profile revealed follicle-stimulating hormone of 0.9 IU/L, luteinising hormone of 0.5 IU/L, hypoestrogenaemia, normal prolactin level, testosterone and DHEA-sulphate at the upper range of normal. Hysterosalpingography showed normal bilateral spillage of dye through the tubes, and a small uterine filling defect. Hysteroscopy was therefore arranged and a small benign uterine polyp was removed. Pelvic ultrasound scan revealed small inactive ovaries. Semen analysis of the male partner was normal. Management options of GnRH pump or gonadotrophin injections were discussed with the patient. She opted for gonadotrophin injections and was therefore commenced on recombinant follicle-stimulating hormone 50 IU (Follitropin beta, Puregon, Organon, The Netherlands) and recombinant luteinising hormone 75 IU (Lutropin alpha, Luveris, Serono, Switzerland) on day two of a withdrawal bleed, induced by a course of oral contraceptive pills. Serial transvaginal ultrasound measurements of follicular growth and endometrial thickness, together with hormonal determination of the levels of estradiol (E2) and luteinising hormone, were used for monitoring of her cycle. The dose of recombinant follicle-stimulating hormone was increased to 75 IU on day 12 of the treatment cycle as there was no obvious follicular growth. Follow up was continued until on day 26 of treatment, when ultrasound scan showed a dominant follicle of 23 mm in diameter, endometrial thickness of 9.1 mm, E2 level of 3155 pmol/L and luteinising hormone level of 3.3 IU/L. Human chorionic gonadotrophin (hCG, 5000 units; Profasi, Serono, Switzerland) was then administered and sexual intercourse was advised. A week later, a serum progesterone of 127 nmol/L confirmed ovulation. The patient became pregnant in this cycle. Unfortunately, the patient miscarried after the six week ultrasound scan and was managed by surgical evacuation of the uterus. Two months later, the patient was very keen to start another treatment cycle. A similar treatment protocol was followed in the second cycle except that the starting dose of recombinant follicle-stimulating hormone was increased to 75 IU. This time, she developed a dominant follicle of 24 mm on day 19 of treatment, endometrial thickness of 10.1 mm, E2 and luteinising hormone level of 2231 pmol/L and 2.4 IU/L, respectively. Serum progesterone was also suggestive of ovulation at 64 nmol/L. Luteal phase support in the form of progesterone suppositories 400 mg daily (Cyclogest, Shire, United Kingdom) was commenced until the day of the pregnancy test. Subsequently, the patient became pregnant, and ultrasound scan performed six weeks later revealed a single viable intrauterine pregnancy. Luteal support was continued until 12 weeks of an ongoing pregnancy. BJOG: an International Journal of Obstetrics and Gynaecology December 2004, Vol. 111, pp. 1481–1484

Effects of follicle-stimulating hormone (FSH) and human chorionic gonadotropin in individuals with an inactivating mutation of the FSH receptor

Objective: To study the gonadal steroid responses to FSH and hCG in individuals with the inherited Finnish-type inactivating Ala189Val mutation of the FSH receptor gene. Design: Prospective clinical and descriptive study. Setting: University hospital. Patient(s): Two women and one man homozygous for the Ala189Val mutation of the FSH receptor gene, and ovarian biopsies from four affected and four healthy women, and four normal fetuses. Intervention(s): Individuals were treated with increasing doses of recombinant FSH (300 IU/day start, 900 IU/day final) and/or a single dose of hCG (5000 IU). Ovarian biopsies were used in immunohistochemical analyses for detection of aromatase cytochrome P450 and transcription factor GATA-4. In situ 3′-end labeling analyses were used for detection of apoptosis. Main Outcome Measure(s): Measurements of serum concentrations of follicle-stimulating hormone, leuteinizing hormone, inhibin A and B, estradiol, testosterone (T), androstenedione, and prolactin, immunostaining for ovarian aromatase, GATA-4, and apoptosis. Result(s): Administration of FSH had no effect on production of the steroids. Similarly, human chorionic gonadotropin (hCG) treatment, alone or after FSH administration, failed to raise serum steroid concentrations. Ovarian apoptosis was absent, and the expression of transcription factor GATA-4 and aromatase was negligible in the ovarian biopsies from Ala189Val homozygous individuals. Conclusion(s): The Ala189Val mutation of the FSH receptor gene results in a complete block of FSH action in vivo. Furthermore, the failure of hCG to increase both ovarian estradiol and testosterone secretion emphasizes the possible contribution of FSH in regulating ovarian androgen synthesis, and supports the concept that both gonadotropins are necessary for appropriate ovarian steroidogenesis in humans.

A double-blind clinical trial comparing a fixed daily dose of 150 and 250 IU of recombinant follicle-stimulating hormone in women undergoing in vitro fertilization

Objective: To determine the efficacy and efficiency of two fixed doses of recombinant follicle-stimulating hormone (FSH) in controlled ovarian hyperstimulation. Design: Randomized, double-blind clinical trial. Setting: Fifteen IVF clinics in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela. Patient(s): Women between 30 and 39 years of age undergoing IVF or intracytoplasmic sperm injection (ICSI). Intervention(s): Daily doses of either 150 IU or 250 IU of recombinant FSH (Puregon) until at least two follicles ≥20 mm were seen on ultrasound. Main Outcome Measure(s): Number of cumulus–oocyte complexes retrieved and total dose of recombinant FSH used. Result(s): Two hundred one women received 150 IU and 203 used 250 IU. In the low-dose group 8.9 oocytes were retrieved compared to 10.2 in the high-dose group (not significant). The 150 IU-treated women received a total of 1,589 IU and the total dose used in 250 IU treated women was 2,492 IU. Implantation rates were 10.0% in the 150 IU group and 10.9% in the 250 IU group. The vital pregnancy rates per started cycle in the low-dose and high-dose groups were 17.1% and 16.7%, respectively. Two women, both in the 250 IU group, were hospitalized because of the ovarian hyperstimulation syndrome (OHSS). Conclusion(s): An increase from 150 IU to 250 IU daily dose of recombinant FSH in women between 30 and 39 years of age has only limited value in augmenting ovarian response.

A prospective randomized clinical trial of differing starter doses of recombinant follicle-stimulating hormone (follitropin-β) for first time in vitro fertilization and intracytoplasmic sperm injection treatment cycles

Objective: Comparison of the efficacy of differing starter doses of recombinant follicle stimulating hormone (rFSH) for IVF and intracytoplasmic sperm injection cycles when the treatment is administered both subcutaneously and intramuscularly. Design: Single center 1-year prospective randomized study. Setting: Academic teaching hospital. Patient(s): 345 couples in first cycle. Intervention(s): Treatment with subcutaneous or intramuscular rFSH, followed by E 2 and ultrasound follicle tracking, with later oocyte collection and zygote transfer. Main Outcome Measure(s): Ovarian response and other clinically dependent variables. Result(s): Group 1 patients, with day-3 FSH levels of less than 8.5 U/L, were randomized to begin treatment with rFSH at 150 IU (n = 146) or 200 IU (n = 151). The total dose of the drugs used was significantly lower in 150 IU group, as was the number of ICSI metaphase II oocytes. No other significant differences found. The dosage was increased in 9% on day 5. Group 2 patients, with day-3 FSH levels of greater than 8.5 U/L, were randomized to treatment with rFSH at 300 IU (n = 24) or 400 IU (n = 24). No significant outcome differences found between the two subgroups. Pregnancy rates for this group were half that of Group 1. Intramuscular administration was significantly more likely to result in a need for increased dosage than was subcutaneous administration. The level of E 2 at the time of hCG treatment was significantly lower in the intramuscular 150 IU group. Conclusion(s): In the main study total dosage used, the ICSI metaphase II oocyte numbers were significantly lower and there was a trend toward a need for a dosage increase on day 5 when 150 IU rFSH was the starter dosage, as compared to a starting dosage of 200 IU. Otherwise, there is little advantage to using the higher dosage.

Prediction of over-response to ovarian stimulation in an intrauterine insemination programme.

Prediction of poor-response is of equal importance to prediction of over-response in intrauterine insemination programmes. The gonadotrophin-releasing hormone agonist (GnRHa) stimulation test (GAST) was assessed as a predictor of over-response to ovarian stimulation in 81 patients. Blood samples were taken on cycle day 2 (before and 24 h after starting the GnRHa). Day 2 and 3 samples were assayed for oestradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Linear and logistic regression analyses were used to assess age, day 2 FSH, day 2 FSH/LH, oestradiol ratio (oestradiol on day 3/oestradiol on day 2) and FSH ratio (FSH on day 3/FSH on day 2) as predictors of the number of follicles (total and > or = 14 mm), oestradiol on HCG day, and clinical pregnancy rate as appropriate. Several parameters were also compared between the patients who produced < or = 3 (> or = 14 mm) follicles (group A) and those who produced >3 (> or = 14 mm) follicles (group B). The mean +/- SEM age of the patients in the study was 32 +/- 0.4 years. The mean total dose of recombinant FSH was 800 +/- 20 IU and the mean duration of stimulation was 7.6 +/- 0.2 days. Nine (11%) and 12 (15%) patients were cancelled for poor and over-response respectively. The oestradiol ratio was significantly positively correlated with oestradiol on HCG day (P < 0.001), and with the number of mature follicles (> or = 14 mm) (P = 0.01). Age, day 2 FSH and FSH ratio were not significantly correlated with oestradiol on HCG day, total follicles and follicles > or = 14 mm. None of the above-mentioned variables was correlated with clinical pregnancy rate. Group A had significantly lower oestradiol ratio (P = 0.007), longer duration of stimulation (P = 0.002), higher total FSH dose (P = 0.001), and lower oestradiol on HCG day (P = 0.001). GAST is therefore useful in predicting the high responders to gonadotrophin stimulation.

In vitro evaluation of aromatase enzyme in granulosa cells using a [ 11C]vorozole binding assay

An in vitro method for measuring aromatase cytochrome P450 enzyme (P450 AROM) in human granulosa cells (GC) has been developed, based on binding of the 11C-labeled aromatase inhibitor vorozole. GC were obtained following superstimulation during in vitro fertilisation. The method revealed a binding affinity ( K d) of 0.4 nM and a maximum binding (B max) at 11 fmol/4000 cells which is equal to 1.6 million binding sites per cell. Linear Scatchard plots indicated a single type of binding site. P450 AROM concentrations measured by [ 11C]vorozole binding correlated positively with aromatisation of [1β- 3H]androst-4-ene-3,17-dione measured as [ 3H]water release, and a positive association was also found with the ovarian in vivo response to follicle-stimulating hormone (FSH) stimulation expressed as 1000 times the ratio of the number of oocytes recovered from a patient and the total dose of recombinant FSH administered. Frozen cells could be used for P450 AROM quantitation, provided the correct freezing procedure was used. Quantitation of P450 AROM, based on binding of [ 11C]vorozole is an accurate and sensitive in vitro method, which might be extended to the measurement of aromatase expression by a noninvasive technique in the intact ovary in vivo using positron emission tomography.

Serum Hormone Concentrations During Treatment with Multiple Rising Doses of Recombinant Follicle-Stimulating Hormone (Puregon) in Men with Hypogonadotropic Hypogonadism

Objective: To study increases of serum FSH and gonadal response in gonadotropin-deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, the Netherlands). Design: An open, prospective, multiple rising dose study in which volunteers received single daily IM doses of recombinant FSH for 3 weeks. The dose administered was increased at weekly intervals: the first 7 days, 75 IU/d; the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d. Participant(s): Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism. Main Outcome Measurement(s): Immunoreactive FSH, LH, inhibin, T, and androstenedione. Result(s): Serum immunoreactive FSH (median) rose in accordance with the recombinant FSH doses administered from 0.5 mIU/mL (range <0.05 to 1.9 mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range 4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks of medication, respectively. The elimination half-life of recombinant FSH was 48 ± 5 hours (mean ± SD), which was slightly longer than that reported after single dose administration of recombinant FSH (32 ± 12 hours). The bioactivity of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22. However, serum FSH and inhibin levels did not correlate when compared after 1, 2, and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T, androstenedione, and E 2 were 0.2 mIU/mL (range <0.05 to 0.7 mIU/mL [conversion factor to SI unit, 1.0]), 58 ng/dL (range <12 to 222 ng/dL [conversion factor to SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit, 0.0349]), and 14 pg/mL (range <14 to 16 pg/mL [conversion factor to SI unit, 3.67]), respectively, at baseline and remained unchanged during the entire treatment period. Conclusion(s): These data indicate that recombinant FSH treatment increases serum FSH in a dose-proportional fashion, increases inhibin secretion, and lacks intrinsic LH activity.