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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.

Background: It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations., Methods: A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used., Results: The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values., Conclusions: Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

Purpose: The purpose of this prospective, randomized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH (rhFSH) alone or in combination with recombinant human LH (rhLH)., Methods: Patients were randomized to receive rhFSH alone (group F; n = 13) or rhFSH + rhLH (group L; n = 15). rhFSH was administered according to a step-down protocol; patients assigned to group L received rhLH at a fixed dose of 75 IU (1 ampoule) throughout the treatment period., Results: The total dose of rhFSH, number of growing follicles, and serum concentrations of estradiol (E2) on the day of hCG administration were similar in both treatment groups. However, the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls. However, when in vitro fertilization (IVF) and intracytoplasmic sperm injection cycles were considered separately, differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF., Conclusions: This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization.

The present study compared ovarian performance and hormone concentrations, after ovulation induction, in polycystic ovarian syndrome (PCOS) patients, using recombinant human FSH (rhFSH) in low-dose step-up and modified step-down regimens. Twenty-six women with clomiphene citrate-resistant chronic anovulatory infertility were treated with rhFSH in two consecutive cycles according to two different low-dose regimens: (i) the classic chronic low-dose step-up protocol, the starting dose being 75 IU; (ii) a modified step-down protocol where the starting dose was 300 IU followed by 3 days free of treatment, then rhFSH 75 IU daily was given and stepwise dose increments were performed exactly the same as in the step-up method. Each woman received both treatment approaches, in a randomized order, with an interval of > or = 1 month between treatments. The total number of follicles that were > 10, > 14 and > 17 mm in diameter on the day of human chorionic gonadotrophin (HCG) administration, and thus cycles with HCG cancelled, were significantly increased with the step-up approach. The total number of rhFSH ampoules tended to be higher with the step-down schedule despite the fact that both the mean duration of treatment and the threshold dose were similar with the two low-dose approaches. A physiological step-down approach for ovulation induction in PCOS patients may be more appropriate in order to avoid multifollicular cycles than the step-up approach.

Recent reports investigating the value of basal inhibin B determination as a predictor of ovarian reserve and assisted reproduction treatment have led to discordant results. This study was undertaken to further assess the relative power of day 3 inhibin B and follicle stimulating hormone (FSH) (defined before treatment) and the woman's age both as single and combined predictors of ovarian response and pregnancy in an in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme. A total of 120 women undergoing their first cycle of IVF or ICSI was included. Forty consecutive cycles cancelled because of poor follicular response were initially selected. As a control group, the nearest completed IVF/ICSI cycles before and after each cancelled cycle (i.e. the closest cycles in temporal relationship to the index cycle) were used. Mean age and basal FSH concentrations were significantly higher in the cancelled than in the control group (P: < 0.01 and P: < 0.001 respectively), whereas basal inhibin B was significantly higher in the latter (P: < 0.05). The association of basal FSH (with an accuracy or predictive value of ovarian response of 79%) with cancellation rate was significant, independent of, and stronger than the effects of age and inhibin B (P: < 0.05). Any two or all three of these variables studied did not improve the predictive value of FSH alone. Woman's age was the only variable independently associated with pregnancy rate. It is concluded that the stronger predictors of success in patients undergoing their first IVF/ICSI treatment cycle are age and basal FSH rather than inhibin B. Basal FSH concentration was a better predictor of cancellation rate than age, but age was a stronger predictor of pregnancy rate.

Purpose: The aim was to compare the follicular response to 37.5 and 50 IU of recombinant follicle-stimulating hormone (FSH) as starting doses for ovulation induction in patients with polycystic ovary syndrome (PCOS)., Methods: Prospective, randomized, crossover study including 15 women with clomiphene citrate-resistant chronic anovulatory infertility. Patients were treated with subcutaneous recombinant FSH at starting doses of 37.5 IU and 50 IU, respectively, according to a low-dose step-up protocol. Each woman received both treatments, in a randomized order, with an interval of > or = 1 month between treatments., Results: All treatment cycles were ovulatory after an appropriate follicular response and hormone levels were similar with both treatments, although the total quantity of FSH required and the mean daily dose required to induce identical follicular development were significantly lower with a starting dose of 37.5 IU FSH. The mean duration of treatment to achieve ovulation was approximately 13 days with both treatments but treatment periods > or = 20 days were required in some patients., Conclusions: In women with PCOS, a starting dose of 37.5 IU recombinant FSH may be adequate to induce follicular growth. However, the use of low starting doses may result in some cases in increased treatment periods and need for monitoring.

Purpose: The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence., Methods: For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP., Results: The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2)., Conclusions: rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

Purpose: Our purpose was to compare ovarian performance and hormonal levels, after ovulation induction, in both normal ovulatory women undergoing intrauterine insemination (group 1) and World Health Organization (WHO) group II anovulatory infertile patients (group 2), using two different gonadotropin drugs., Methods: Patients (n = 20 per group) were treated during consecutive cycles, using the same stimulation protocol, with highly purified urinary FSH (HP-FSH) in the first treatment study cycle and recombinant FSH (rFSH) in the second one. Patients in group 1 were treated according to a late low-dose technique, and WHO group II anovulatory patients (group 2) received chronic low-dose FSH therapy., Results: Compared with HP-FSH, treatment with rFSH in group 2 required significantly less ampules of drug to induce follicular development but resulted in significantly higher plasma levels of estradiol and inhibin A on the day of human chorionic gonadotropin injection. No differences were found when both treatment modalities were compared in group 1., Conclusions: rFSH is more efficacious than urinary HP-FSH for ovulation induction in WHO group II anovulatory infertile patients as assessed by follicular development, hormonal levels, and the amount of FSH required.

Objective: Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the woman's age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used., Study Design: The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used., Results: The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone., Conclusion: Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.

The use of pure follicle stimulating hormone (pFSH) and highly purified FSH (FSH-HP) versus the combinations pFSH/human menopausal gonadotrophin (HMG) and FSH HP/HMG, respectively, was compared for stimulating follicular development after gonadotrophin-releasing hormone agonist (GnRHa) suppression in women undergoing in vitro fertilization (IVF)-embryo transfer. Two consecutive prospective, randomized studies were carried out at the Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. Two groups of 188 (study 1) and 252 (study 2) consecutive infertile patients respectively, scheduled for IVF-embryo transfer were included. Pretreatment with leuprolide acetate (long protocol) was followed by gonadotrophin treatment in all patients. In study 1, 92 patients received i.m. pFSH alone (group pFSH) and 96 were treated with the combination of i.m. pFSH and i.m. HMG (group HMG-1). In study 2, 123 patients received s.c. FSH-HP alone (group FSH-HP) and 129 patients were given the combination of s.c. FSH-HP and i.m. HMG (group HMG-2). Main outcome measures included follicular development, oocyte retrieval, fertilized oocytes, duration and dose of gonadotrophin therapy, and clinical pregnancy. There were no significant differences between pFSH and pFSH/HMG nor between FSH-HP and FSH-HP/HMG cycles with regard to the number of ampoules of medication used, day of human chorionic gonadotrophin (HCG) administration, mean peak serum oestradiol concentrations, number of follicles punctured, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that urinary FSH (either purified of highly purified) alone is as effective as the conventional combination of urinary FSH/HMG for ovarian stimulation under pituitary suppression in IVF cycles. Therefore, they can be used interchangeably in IVF programmes.

At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results.

Fifteen infertile women with inadequate luteal phase, histologically documented in at least two separate cycles, and normal midluteal plasma levels of progesterone (greater than or equal to 10 ng/mL), estradiol (70 to 300 pg/mL), and prolactin (less than 20 ng/mL) received "pure" follicle-stimulating hormone (pFSH), 150 IU intramuscularly, for 4 days (days 1 to 4 of the cycle). The endometrial defect was corrected in 7 of the 15 (46.7%) patients during the first treated cycle. Hormonal levels were similar in control and treatment cycles. Two of 5 patients with no additional infertility factors except luteal phase deficiency (LPD) became pregnant and carried to term singleton pregnancies. In 5 additional infertile patients with normal luteal function as assessed by endometrial histological study (2 cycles) and hormone measurements (first study cycle), a third biopsy was performed in a consecutive cycle under pFSH administration. In no case was the normal secretory pattern impaired. It is concluded that (1) some forms of LPD may be successfully treated by early follicular pFSH therapy and (2) pFSH does not alter the normal endometrial secretory pattern.