Follicle-stimulating Hormone Cycles Research Articles

Response to ovulation induction treatments in women with polycystic ovary syndrome as a function of serum anti-Müllerian hormone levels.

To assess whether anti-Müllerian hormone (AMH) can predict response to ovulation induction (OI) with clomiphene citrate (CC), letrozole (LET), or follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS) undergoing OI/intrauterine inseminations (IUI). A total of 738 OI/IUI cycles from 242 patients at an academic center were stratified in three groups by medication: CC (n = 295), LET (n = 180), and FSH (n = 263), in a retrospective fashion. Ovarian response to treatment (RT, development of at least one dominant follicle) was assessed using mixed effects logistic regression models. Overall, RT cycles had lower AMH levels compared to no-RT cycles (p < 0.001). This finding persisted when analysis was limited to oral agents but attenuated in FSH cycles. For CC and LET cycles, the predicted probability (PProb) for RT decreased as AMH levels increased (PProb (95%CI): 97% (93-100), 79% (70-88), and 75% (61-89); 85% (78-93), 75% (67-83), and 73% (63-86) for AMH pct.: ≤ 25th, ≥ 50th, and ≥ 75th, for CC and LET, respectively)). However, RT was noted in 98.5% of FSH/IUI cycles regardless of AMH. For CC cycles, those with AMH ≥ 75th pct. had lower odds for RT over cycles with AMH < 75th pct. (OR 0.2, 95%CI 0.04-0.8, p = 0.02). Similarly, lower odds for RT were observed in LET cycles with AMH ≥ 75th pct. (0.6, 0.3-1.4, p = 0.25). In PCOS, increasing serum AMH levels are associated with lower probability of RT to oral agents. Our findings constitute a valuable tool for the clinician when counseling PCOS patients and designing a personalized ovulation induction treatment strategy.

Success Rates of Clomiphene Citrate and Recombinant Gonadotropin Cycles: A Single-Center Experience

Objective: This aim of this study is to assess the ovulation induction cycles based on clomiphene citrate and gonadotropin administration and specify the factors associated with successful outcomes. Study Design: This is a prospective study of 631 patients who underwent 917 ovulation induction cycles. While clomiphene citrate was used in 680 cycles (74.2%) and recombinant follicle-stimulating hormone was administered in 237 cycles (25.8%). Results: A total of 153 pregnancies were achieved in 917 ovulation induction cycles, indicating a clinical pregnancy rate of 16.7%. The ovulation induction cycles which ended up with clinical pregnancy had a significantly lower frequency of smoking (p=0.005), shorter infertility duration (p=0.001), higher basal luteinizing hormone (p=0.021) and lower basal progesterone (p=0.008) than unsuccessful cycles. The clomiphene citrate cycles which ended up with clinical pregnancy had a significantly lower frequency of smoking (p=0.011), shorter infertility duration (p=0.001) and lower basal progesterone (p=0.013) than the unsuccessful cycles. The recombinant follicle-stimulating hormone cycles which ended up with clinical pregnancy had a significantly higher basal luteinizing hormone (p=0.008) than the unsuccessful cycles. Basal luteinizing hormone and progesterone concentrations could significantly distinguish the patients who were able to conceive in ovulation induction cycles (p=0.021 and p=0.008, respectively).Conclusions: Smoking, longer duration of infertility, and elevated basal progesterone are poor prognostic factors for clinical pregnancy in clomiphene citrate and recombinant follicle-stimulating hormone cycles.

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

Letrozole Versus Recombinant FSH in Ovulation Induction for Intrauterine Insemination in Patients With Polycystic Ovarian Syndrome

To compare the efficiency of the aromatase inhibitor Letrozole with follicle-stimulating hormone (FSH) , for ovulation induction in patients with polycystic ovarian syndrome (PCOS) undergoing intrauterine insemination (IUI). Monocentric comparative retrospective study. Analysis of 106 cycles of IUI performed in our institution between January 1st, 2003 and December 31st, 2004 in patients with PCOS (according to the Rotterdam consensus parameters). Of them, 31 cycles used Letrozole for ovulation induction and 75 cycles employed recombinant FSH. The Letrozole cycles were induced with 5 mg a day, starting on day 2 or day 3 of cycle for 5 days. Recombinant FSH cycles were induced with a daily dosis of 50 -150 IU/day according to patient’s body mass index from cycle day 3 until hCG administration. HGC was given when a leading follicle reached 17 mm of mean diameter. Two IUIs were performed, 12 and 36 hours after hCG administration. Cancellation, pregnancy per IUI and per started cycle, multiple pregnancy, miscarriage and take home rates were compared between both groups. No significant differences were observed between both groups in terms of pregnancy rates per started cycle or per IUI, although slightly better outcome was obtained with letrozole. However, as cancellation and miscarriage rates were higher (although not significant) in the Letrozole group, the take home baby rate per started cycle was comparable between both groups. Tabled 1 The use of Letrozole for ovulation induction in PCOS women for IUI provides similar outcome in terms of take home baby rate per started cycle than the use of recombinant FSH.

Concentrations of follicle-stimulating hormone correlate with alkaline phosphatase and a marker for vitamin K status in the perimenopause.

Serum alkaline phosphatase (ALP), a gross marker of bone turnover, has been reported to be elevated after menopause, a period characterized by hallmark increases in follicle-stimulating hormone (FSH). Whether the ALP rise coincides with the perimenopausal transition when changes in FSH, estrogen levels, and menstrual cycles are first apparent is not known. The purpose of this cross-sectional study was twofold: (1) to characterize the influence of the perimenopausal transition on ALP activity and (2) to correlate ALP activity with more precise markers for bone, osteocalcin (OC), and vitamin K status assessed with undercarboxylated osteocalcin (ucOC). Thirty-eight studies of hourly FSH were conducted on cycle day 6 of the follicular phase in perimenopausal women volunteers, aged 40-54 years (mean body mass index [BMI] = 24.2 +/- 0.5). Mean FSH was used to define the perimenopausal stage (early perimenopausal, mean FSH </= 15 IU/L, n = 27; late perimenopausal, mean FSH > 15 IU/L, n = 11). As expected, late perimenopausal women had irregular and longer menstrual cycles, lower estradiol (E(2)) and estrone (E(1)) levels, and a lower frequency of ovulations vs. the early group. ALP was higher (76.5 +/- 8.3 vs. 58.3 +/- 2.7 IU/L, p = 0.045) compared with the early perimenopausal group. In a subsample (n = 10), OC was associated with ALP (r = 0.69, p < 0.03), FSH was positively related to ucOC concentrations (r = 0.7, p < 0.03), and women with E(1) concentrations <40 pg/ml had double the percentage of ucOC compared with those where E(1) was >40 pg/ml (46.3% +/- 6.6% vs. 22.0% +/- 3. 1%, p < 0.006). Clinical markers of the perimenopause are associated with a nonspecific but inexpensive marker of enhanced bone turnover (i.e., higher ALP) and correlate well with more precise markers of bone activity. These findings suggest that health-promotion strategies for preserving bone should be instituted well before the last menstrual period.

Luteinizing hormone response to gonadotrophin-releasing hormone in normal women undergoing ovulation induction with urinary or recombinant follicle stimulating hormone

Oestradiol enhances pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) in normal women, while in women undergoing ovulation induction the putative factor gonadotrophin surge attenuating factor (GnSAF) attenuates the response of luteinizing hormone (LH) to GnRH. To study the relationships between oestradiol and GnSAF during ovulation induction, 15 normally ovulating women were investigated in an untreated spontaneous cycle (control, first cycle), in a cycle treated with daily i.m. injections of 225 IU urinary follicle-stimulating hormone (FSH) (Metrodin HP, uFSH cycle) and in a cycle treated with daily s.c. injections of 225 IU recombinant FSH (Gonal-F, rFSH cycle). Treatment with FSH started on cycle day 2. The women during the second and third cycle were allocated to the two treatments in an alternate way. One woman who became pregnant during the first treatment cycle (rFSH) was excluded from the study. In all cycles, an i.v. injection of 10 microg GnRH was given to the women (n = 14) daily from days 2-7 as well as from the day on which the leading follicle was 14 mm in diameter (day V) until mid-cycle (n = 7). The response of LH to GnRH at 30 min (deltaLH), representing pituitary sensitivity, was calculated. In the spontaneous (control) cycles, deltaLH values increased significantly only during the late follicular phase, i.e. from day V to mid-cycle, at which time they were correlated significantly with serum oestradiol values (r = 0.554, P < 0.01). Initially during the early follicular phase in the uFSH and the rFSH cycles, deltaLH values showed a significant decline which was not related to oestradiol (increased GnSAF bioactivity). Then, deltaLH values increased significantly on cycle day 7 and further on day v with no change thereafter up to mid-cycle. On these two days, deltaLH values were correlated significantly with serum oestradiol values (r = 0.587 and r = 0.652 respectively, P < 0.05). During the pre-ovulatory period, deltaLH values in the FSH cycles were significantly lower than in the spontaneous cycles. Significantly higher serum FSH values were achieved during treatment with uFSH than rFSH. However, serum values of oestradiol, immunoreactive inhibin, and deltaLH as well as the number of follicles > or = 12 mm in diameter did not differ significantly between the two FSH preparations. These results suggest that in women undergoing ovulation induction with FSH, oestradiol enhances pituitary sensitivity to GnRH, while GnSAF exerts antagonistic effects. The rFSH used in this study (Gonal-F) was at least as effective as the uFSH preparation (Metrodin-HP) in inducing multiple follicular maturation in normally cycling women.

Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone.

It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women.

Modulation of the action of gonadotrophin surge-attenuating factor by gonadotrophin-releasing hormone

Gonadotrophin surge-attenuating factor (GnSAF) is a putative non-steroidal ovarian factor which attenuates the luteinizing hormone (LH) surge in superovulated women through the reduction of the pituitary response to gonadotrophin-releasing hormone (GnRH). The mechanism of action of GnSAF on gonadotrophin secretion was further studied by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. The response of the pituitary to five consecutive pulses of GnRH was investigated in late follicular phase (follicle size 15 mm) of both cycles. GnRH pulses, 10 micrograms each, were injected i.v. every 2 h and LH was measured in blood samples taken before and 30, 60 and 120 min after each pulse. FSH was injected daily at the fixed dose of 225 IU starting on cycle day 2. Peak values of LH increment occurred 30 min after each pulse. However, maximal LH increment occurred in both cycles after the second GnRH dose. In the FSH cycles the response of LH to the first three pulses was significantly attenuated compared with the spontaneous cycles, while the response to the fourth and fifth pulses was similar in the two cycles. In both cycles, LH increment 30 min post GnRH (net increase above the previous value) was similar after the fourth and fifth pulses. Serum concentrations of oestradiol and immunoreactive inhibin, although higher in the FSH cycles, remained stable throughout the GnRH experimental period in both cycles. These results demonstrate that multiple submaximal doses of GnRH can override the attenuating effect of GnSAF on LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of gonadotrophin surge-attenuating factor during the luteal phase in superovulated women

Gonadotrophin surge-attenuating factor (GnSAF) is a putative nonsteroidal ovarian factor that attenuates the luteinizing hormone (LH) surge in superovulated women. GnSAF bioactivity was studied during the luteal phase by investigating six normally ovulating women in two cycles--a spontaneous and a follicle-stimulating hormone (FSH)-treated cycle. In both cycles, the pituitary response to an acute intravenous injection (10 micrograms) of luteinizing-hormone-releasing hormone (LHRH) was investigated in late follicular (follicle size 16 mm), early luteal (day 5 after human chorionic gonadotrophin, hCG), midluteal (day 9 after hCG) and late luteal phase (day 12 or 13 after hCG). FSH was injected daily at the dose of 225 iu on cycle days 2, 3 and 4, and 150 iu thereafter. The increase in LH and FSH (mean +/- SEM) 30 min after LHRH in the spontaneous cycles decreased significantly from early to late luteal phase and remained unchanged in the FSH-treated cycles. Increases in LH and FSH 30 min after LHRH were significantly attenuated in the FSH-treated compared with the spontaneous cycles in late follicular and luteal phases. Serum oestradiol and progesterone concentrations were significantly higher in the FSH than in the spontaneous cycles only in early, but not in mid- and late luteal phase. The pattern of serum oestradiol and progesterone changes during the luteal phase did not correlate with the increases in LH and FSH 30 min after hCG both in the spontaneous and the FSH cycles. These results suggest that GnSAF bioactivity is high during the luteal phase of superovulated cycles.

Polycystic ovary syndrome: low-dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyper-responsive patients.

We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to clomiphene citrate, who had a previous history of multifollicular ovarian development on gonadotrophin stimulation. Each woman had one cycle of gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low-dose FSH protocol, 10 cycles were unifollicular, while two to three follicles were observed in nine cycles, and four cycles were multifollicular. The ovarian hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and increasing FSH levels, androgen levels increased during stimulation on both protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies following the FSH cycles. In conclusion, low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate even in PCOS women with a previous record of multifollicular ovarian development.

Blunted prolactin response to exogenous luteinizing hormone releasing hormone in superovulated women

To investigate the prolactin (PRL) response to luteinizing hormone releasing hormone (LHRH) in superovulated cycles, eight normally ovulating women were studied in two cycles, i.e. a spontaneous (control) and a cycle treated with 'pure' follicle stimulating hormone (FSH) (225 IU/day). LHRH was given to the women i.v. (a single injection of 100 micrograms) in the late follicular phase of both cycles. The oestradiol levels (mean +/- SEM) at the time of the LHRH challenge were 635 +/- 31 and 1707 +/- 225 pmol/l respectively (P less than 0.001). The size of the leading follicle was similar in both cycles. Basal PRL levels (mean +/- SEM) on the day of the LHRH experiment were significantly higher in the FSH (250 +/- 31 microIU/ml) than in the spontaneous cycles (133 +/- 15 microIU/ml. P less than 0.05). In the latter cycles, LHRH induced a significant increase in serum PRL and LH levels, while the FSH cycles, the prolactin (PRL) response to LHRH was blunted and LH response markedly attenuated. We conclude that superovulation induction stimulates basal but suppresses LHRH-induced PRL release. It is suggested that basal PRL secretion is LHRH-independent and the suppressing effect is mediated via previously described paracrine interactions between the gonadotrophs and lactotrophs and/or through ovarian inhibitory substances.

The importance of follicle-stimulating hormone increase for folliculogenesis

To study the role of the increase in follicle-stimulating hormone (FSH) during the early follicular phase of the menstrual cycle in folliculogenesis, eight normally cycling women were investigated in a spontaneous cycle (n = 8), a cycle treated with clomiphene citrate (n = 8), a cycle treated with FSH (n = 8) and a cycle treated with FSH plus pulsatile luteinizing-hormone-releasing hormone (LHRH) (n = 5). In the FSH and the FSH plus LHRH cycles, the leading follicle reached the size of 18 mm 2 days earlier on average than in the clomiphene-treated cycles. However, the rate of growth of the leading follicle was similar in the stimulated and the spontaneous cycles. At the same time, circulating levels of FSH differed greatly among the different groups of cycles. During the early follicular phase, serum FSH levels were significantly higher in the FSH plus LHRH and the FSH cycles than in the clomiphene and the spontaneous cycles. We conclude that the preovulatory stage of the dominant follicle is advanced by high FSH levels in the early follicular phase of the cycle. It is suggested that FSH controls follicle development in women at the recruitment--selection stage.

Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression

This study compares the use of human menopausal gonadotropin (hMG) versus follicle-stimulating hormone (FSH), after gonadotropin-releasing hormone agonist (GnRH-a) suppression for in vitro fertilization. Thirty-seven patients were randomized to ovarian stimulation with either hMG or pure FSH. The GnRH-a leuprolide acetate was administered to all patients beginning in the midluteal phase of the prior cycle and continuing until the day of human chorionic gonadotropin (hCG) administration. There were no significant differences between hMG and FSH cycles with regard to the day of hCG administration, mean peak estradiol levels, number of ampules of medication used, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that there is no significant difference between hMG and FSH stimulation when used in conjunction with GnRH-a.

Seasonal cycles in gonadal activity and plasma gonadotropin in the musk turtle, Sternotherus odoratus

Plasma gonadotropin cycles were examined in relation to the seasonal gonadal cycle in freshly captured musk turtles, Sternotherus odoratus, from South Carolina. Acute and chronic stress effects of captivity on testicular growth and circulating plasma testosterone (T) and follicle-stimulating hormone (FSH) also were examined. Monthly mean FSH levels in freshly captured males were correlated significantly with plasma T. Both T and FSH were minimal in spring when testes were small, and highest in the fall in males that had begun spermiation and whose testes had begun to regress. Individual plasma T and FSH values were significantly correlated during the fall when both hormones were at elevated levels. In contrast, plasma luteinizing hormone (LH) remained undetectable throughout the year in males. Females had nondetectable levels of both plasma LH and FSH throughout the year. There was a seasonal pattern in plasma 17β-estradiol which was correlated with follicular growth. Holding males in captivity (outdoors) reduced plasma T by 35–60% within 24 hr of capture (depending on season) and plasma T remained at these lower levels after 2 weeks. However, FSH was not significantly affected by such short-term “stress.” Testicular weight and FSH cycles of captive males were similar to those of males in the field. Monthly plasma T of long-term captives also exhibited a seasonal cycle but at a level significantly lower than in the field and with a delayed peak. Thus, while the data suggest that FSH may be important to both seasonal testicular growth and androgen secretion, fluctuations in FSH alone cannot account for all observed patterns or changes in spermatogenesis or plasma androgen levels.