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PubMed1996

[Ovulation induction with pure FSH in anovulatory patients resistant to clomifene citrate].

The objective was to evaluate the utility of the pure FSH as treatment of women clomiphene-resistant. Seventy two patients clomiphene-resistant were treated with pure FSH. Ovulation induction was started with 75 IU of pure FSH on day 3 of the menstrual cycle, monitoring the follicular growth with transvaginal ultrasonography, additional doses of pure FSH were administered accordingly. Human chorionic gonadotropin (10,000 IU) was administered when the dominant follicle reached a diameter > or = 16 mm. The pregnancy rate per cycle was 18.0%, on the other hand, the cumulate rate of pregnancy was 72.2%. There was not significant difference in the pregnancy rate between patients with primary or secondary infertility. The rate of spontaneous abortions was similar to the general population. As conclusion, it therefore appropriate to offer the treatment with pure FSH to patients clomiphene-resistance. The cases with gonadotropin-resistance, will be candidates to surgical procedures.

Adolescent↗
PubMed1979

Ovulation induction in amenorrheic women.

Seventy-six patients with primary or secondary amenorrhea who wished to conceive were treated with clomiphene citrate, 2-Br-alpha-ergocryptine, and/or human menopausal gonadotropins (hMG). Of these 71 patients who received clomiphene citrate, 39 (55%) ovulated. Of these 71 patients, 52 had withdrawal uterine bleeding following IM progesterone, and 38 (73%) ovulated; only 1 of the 19 who did not bleed ovulated (P less than 0.001). Ovulation occurred in the former group of patients whether or not they had galactorrhea. Of the 32 patients who failed to ovulate despite treatment with the maximal dose of clomiphene, 250 mg/day for 5 days, 26 received hMG-hCG. All 26 ovulated and 15 conceived. All 8 patients with amenorrhea-galactorrhea who were treated either primarily or secondarily with bromergocryptine ovulated, and 4 conceived. Therefore, the drug of choice for ovulation induction in amenorrheic patients depends on 1) the presence of withdrawal bleeding after progesterone and 2) the presence of galactorrhea. In all patients with progesterone withdrawal bleeding with or without galactorrhea, the initial treatment of choice is clomiphene citrate. In the absence of withdrawal bleeding, hMG should be administered if galactorrhea is absent, and bromergocryptine should be administered if galactorrhea is present.

Amenorrhea↗
PubMed1988

[The significance of specific LH patterns before and following ovulation induction with hCG within the scope of in vitro fertilization and simplified diagnosis].

In 55 patients follicular stimulation for in vitro fertilisation (IVF) was carried out with a combination of clomiphene (Cl)/human follicle stimulating hormone (FSH) and human chorion gonadotropin (hCG) for ovulation induction. Two days before the anticipated hCG application LH measurements in 4-hourly urine samples were started and continued until follicular aspiration. A LH-IRMA (LH-MAIAclone, Serono) utilising monoclonal antibodies enabled the detection of LH also after hCG. In order to facilitate the organisation and to exclude sources of error the LH concentrations were correlated to the urinary creatinine concentrations and expressed as LH units per gram creatinine (LH U/g Cr). 6 characteristic LH profiles could be found: 31 patients (group a) had a baseline between 5-12 LH U/g Cr with an abrupt increase 10-12 hours after hCG, 2 patients (group b) had slightly elevated LH levels (10-15 LH U/g Cr), after hCG a decrease and 20-30 hours later a distinct increase. 7 patients (group c) had an endogenous LH surge before the hCG application. 3 patients (group d) had very low LH values (below 5 LH U/g Cr), 6 patients (group e) markedly increased concentrations (above 20 LH U/g Cr) with no change after hCG. 6 patients (group f) had significant LH fluctuations. Of the 15 pregnancies 12 were in group a, 2 in group b, 1 in group c, none in the groups d-f. The good correlation between the LH concentrations and creatinine concentrations in the urine proved the usefulness of this method and contributed well to organisational simplifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗
PubMed1990

Progesterone:estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction.

UNLABELLED: The purpose of this study was to compare progesterone (P):estradiol (E2) ratios after ovulation induction at the time of implantation in cycles resulting in ongoing pregnancies or abortions and in nonconception cycles. Material included 43 stimulated conception cycles, 29 with human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG), 14 with clomiphene citrate (CC) with or without hCG, and 28 nonconception cycles (13 hMG and hCG, 15 CC with or without hCG). Midluteal P and E2 were measured and expressed in ng/mL. There were no differences in P:E2 ratios (mean +/- SE) for ongoing pregnancies after hMG and hCG (n = 20, 112.6 +/- 14.9), CC and hCG (n = 6, 97.0 +/- 15.9), or CC alone (n = 5, 96.2 +/- 25.5), and the data were pooled. Progesterone:estradiol ratios in 31 ongoing pregnancies and 28 nonconception cycles were 107.0 +/- 10.7 and 115.2 +/- 12.5, respectively, both significantly higher than in 12 abortions (64.5 +/- 13.2). IN CONCLUSION: (1) P:E2 ratios at the time of implantation were similar after CC with or without hCG and hMG and hCG treatment; (2) high luteal P:E2 ratio was associated with ongoing pregnancies; and (3) lower P:E2 ratio was seen in cycles leading to spontaneous abortion.

Abortion, Spontaneous↗
PubMed1997

Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction programme.

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.

Adult↗
PubMed1986

Estradiol and hemodynamics during ovulation induction.

Left ventricular size and stroke volume increase in human pregnancy and during estrogen administration in laboratory animals. In order to determine if elevated levels of endogenous estrogens in humans produce hemodynamic changes similar to those that occur during pregnancy, 14 patients were studied during ovulation induction at day 8 +/- 2 (SD) (proliferative phase) and at day 14 +/- 4 (midcycle) of their cycles. M-mode echocardiography was carried out with the patient in the left lateral decubitus, head down and head up positions. The mean serum estradiol level was 294 +/- 234 (SD) pg ml-1 at day 8 +/- 2 (treatment day) and it increased to 1503 +/- 531 pg ml-1 at day 14 +/- 4 (cycle day) of the same cycle. This change in serum estradiol was significant (P less than 0.001), associated with an increase in left ventricle diastolic dimension of 2.3 +/- 1.1 mm (P less than 0.001). During the same time period stroke volume and cardiac index correspondingly increased. Heart rate, fractional shortening, and blood pressure did not change and systemic vascular resistance decreased. Many of the cardiovascular adaptations of pregnancy are duplicated by high levels of endogenous estrogens and these changes are evident in as few as 6 days. Thus, we conclude that changes in endogenous estrogen correlate with certain cardiovascular parameters, the most striking of which is the left ventricular size. This may be one of the adaptive mechanisms by which the maternal circulation adapts to pregnancy.

Adult↗
PubMed2000

Recombinant human follicle-stimulating hormone for ovulation induction in polycystic ovary syndrome: a prospective, randomized trial of two starting doses in a chronic low-dose step-up protocol.

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.

Adult↗
PubMed2003

Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: Metformin has been used as a treatment in many studies of the infertility associated with polycystic ovary syndrome (PCOS). We will review the literature on this topic as it specifically relates to changes in body mass index (BMI), improvement in menstrual cyclicity, and effects on ovulation and pregnancy rates. DESIGN: Review of studies addressing biochemical and clinical changes in women with PCOS on metformin. MAIN OUTCOME MEASURE(S): Changes in BMI, menstrual cyclicity, ovulation rate, and pregnancy rate. RESULT(S): Metformin has been shown to produce small but significant reductions in BMI. Multiple observational studies have confirmed an improvement in menstrual cyclicity with metformin therapy. The studies addressing the concomitant use of metformin with clomiphene citrate initially predicted great success, but these have been followed by more modest results. There is little data in the literature concerning the use of metformin and hMGs. CONCLUSION(S): Some (but not all) women with PCOS have improvements in their menstrual cycles while on metformin. The data supporting the use of metformin in ovulation induction with clomiphene citrate and hMG remain to be confirmed by large, randomized, prospective studies.

Body Mass Index↗
PubMed1996

Immunoreactive endothelin-1, endothelin-2 and big endothelin-1 in follicular fluids of women undergoing ovulation induction for in-vitro fertilization.

Endothelin-like immunoreactivity specific for endothelin-1 (ET-1), endothelin-2 (ET-2) or big endothelin-1 (big ET-1) was measured, using commercially available radioimmunoassay kits, in follicular fluid collected at the time of oocyte aspiration from 36 women undergoing ovulation induction by human menopausal gonadotrophin (HMG). The relationship of ET concentrations to HMG dose, peak serum oestradiol concentration, the number and size of follicles (by ultrasound), the number of retrieved oocytes and the fertilization rate per retrieved oocyte were studied. Overall, 94% of follicular fluid samples were positive for ET-1, 92% were positive for ET-2, and 100% were positive for big ET-1. Mean ET-1, ET-2 and big ET-1 concentrations were 17.23 +/- 12.20, 32.42 +/- 14.32 and 34.55 +/- 16.34 pg/ml respectively. Endothelin-like immunoreactivity in follicular fluid samples was found in an order of ET-1 < ET-2 < big ET-1. There was a highly significant positive correlation (r = 0.8711,P = 0.001, n = 32) between follicular ET-1 and ET-2 concentrations. No significant correlation of follicular big ET-1 was established either with ET-1 or ET-2. However, big ET-1 was found to be negatively correlated with number of oocytes (P = 0.03) and number of follicles (P = 0.04). Control plasma ET-1 and follicular ET-1 were not significantly different. There was no significant correlation between ET concentrations and any of the other studied parameters. The results demonstrated that immunoreactive ET-1, ET-2 and big ET-1 exist in human follicular fluid collected at the time of oocytes retrieval for in-vitro fertilization and may be involved in the regulation of reproductive function. The clinical significance and physiological role of follicular fluid ET deserve further studies.

Adult↗
PubMed1993

Combined bilateral tubal and multiple intrauterine pregnancy after ovulation induction.

Over the last 20 years, the frequency of multiple pregnancy has increased mainly because of the introduction of exogenous pituitary gonadotropins in the treatment of sterility. The incidence of ectopic pregnancies also increased during the same period of time. This paper describes the first reported case of a simultaneous bilateral tubal and multiple intra-uterine pregnancy after ovulation induction with human gonadotropins.

Abortion, Induced↗
PubMed2003

Inhibin B levels on cycle day 3 to predict the ovulatory response in women with PCOS undergoing ovulation induction via low dose step-up gonadotropin protocol.

BACKGROUND: In this prospective clinical single blind study, we aimed to investigate whether day 3 serum inhibin B levels in women with polycystic ovarian syndrome(PCOS) are of predictive value for the estimation of the ovarian response to gonadotropins. METHODS: Ovulation induction with low dose step-up gonadotropin protocol, starting with 75 IU/day, was performed for 30 cycles on 25 patients with PCOS. Day 3 serum inhibin B, follicle-stimulating hormone(FSH) and estradiol, and midluteal serum progesterone levels were measured during each cycle. The correlations between day 3 inhibin B levels and day 3 FSH, day 3 estradiol and midluteal progesterone measurements, as well as the amount of gonadotropin required to provide an ovulatory cycle were investigated. RESULTS: Five (27.8%) out of 18 cycles with day 3 inhibin levels <50.0 pg/ml; and 11 (91.7%) out of 12 cycles with levels > or = 50.0 pg/ml were ovulatory (chi(2)=9.38, p<0.01). Moreover, day 3 inhibin B levels had statistically significant negative correlation with the gonadotropin used; and significant positive correlation with the midluteal progesterone levels (p<0.05). There wasn't any significant relation between day 3 FSH and estradiol levels with the gonadotropin used and progesterone levels. CONCLUSIONS: It has been observed that as day 3 serum inhibin B levels increased in women with PCOS, the ovulatory response to gonadotropins and the rate of ovulatory cycles increased significantly.

Adult↗
PubMed1999

Lack of the predominant BRCA1 and BRCA2 mutations in Jewish ovarian carcinoma patients who previously underwent ovulation induction.

The objective of the present investigation was to assess the presence of BRCA mutations in ovarian carcinoma patients who were previously treated with fertility drugs. The presence of the predominant Jewish BRCA1 and BRCA2 mutations in archival paraffin-embedded tumor tissue of four Jewish women with ovarian carcinoma who previously underwent ovulation induction with clomiphene citrate, was determined. None of the tissues contained the mutations examined. This preliminary finding does not support the assumption that the presence of BRCA1 and BRCA2 mutations in some infertility patients treated by fertility drugs could explain the subsequent development of epithelial ovarian cancer in these women.

Adult↗
PubMed1987

[Transient hyperprolactinemia during ovulation induction with gonadotropin releasing hormone (GnRH) pulsatile administration].

Seven clomiphene-resistant normoprolactinemic anovulatory patients were treated with GnRH pulsatile administration (total 15 treatment cycles). Several problems with GnRH pulse therapy were raised through 6 unsuccessful cases. In 5 cases (10/15 treatment cycles), transient hyperprolactinemia (50-100 ng/ml) appeared immediately after the initiation of the treatment and persisted for 6-10 days. Follicle maturation and ovulation was not induced in these cases. Frequent blood sampling failed to demonstrate GnRH-induced LH secretion in 3 cases. Synchronous secretion of PRL with LH was observed when serum PRL levels were low, but not in situations with elevated serum PRL levels. The lack of GnRH-induced LH secretion indicates the down-regulation of the pituitary with increased frequency of GnRH pulses due to intrinsic and exogenous GnRH. The synchrony of LH and PRL suggests the contribution of GnRH-mediated PRL releasing factor (PRF) through a paracrine system between gonadotrophs and lactotrophs. Transient hyperprolactinemia observed in the current study might be attributable to a relative increase in GnRH to a GnRH-associated peptide (GAP), a constituent of GnRH prohormone and possessing an intrinsic effect of PRL suppression, by exogenously administered GnRH, causing overwhelming superiority of GnRH-mediated PRF. Transient hyperprolactinemia and regulation of the pituitary may hamper ovulation induction with GnRH pulse therapy when applied to cases with intact hypothalamic-pituitary axis.

Anovulation↗
PubMedDate not supplied

Effect of body mass index and follicular synchrony in the ovarian response to ovulation induction with menotropins.

OBJECTIVE: To determine the correlation between body mass index, follicular synchrony, and pregnancy rate in a controlled ovarian hyperstimulation program with menotropins. SUBJECTS AND METHODS: Seventy-nine hyperstimulation cycles were evaluated. Transvaginal ultrasonographic control was performed and 10,000 IU of human chorionic gonadotropin were administered when the dominant follicle reached a diameter > 16 mm. In order to evaluate the follicular response, the ovarian synchrony factor was used (# follicles > or =16 mm/# follicles > 10 mm). For the statistical analysis, linear correlation and chi-square tests were used. RESULTS: When patients had a normal body mass index there was a positive correlation ( r = .52) between body mass index (kg/m(1.5)) and the ovarian synchrony factor. Weight deficiency and obesity had a deleterious effect on the ovarian response ( r = -.47 and r = -.77, respectively). There was a significant difference in the number of pregnancies in patients with ideal weight in relationship to the subgroup with weight deficit. CONCLUSIONS: An adequate body constitution increases the possibilities of achieving success in ovulation induction programs; on the other hand, weight disturbances have a deleterious effect on ovulation.

Body Mass Index↗
PubMed1988

Combined gonadotropin-releasing hormone analog and exogenous gonadotropins for ovulation induction in infertile women: efficacy related to ovarian function assessment.

The ovarian function of infertile women with normal menstrual rhythm was investigated by daily plasma hormone (estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone) analyses throughout the menstrual cycle, and patients were diagnosed as showing a subnormal profile of progesterone in the early luteal phase or as showing no abnormality. Women with oligomenorrhea and elevated luteinizing hormone levels were diagnosed as having polycystic ovary syndrome primarily on the basis of endocrinology. All patients were treated with a gonadotropin-releasing hormone analog to suppress endogenous luteinizing hormone and follicle-stimulating hormone so that ovulation induction with exogenous gonadotropins could be undertaken as in patients with hypogonadotropic hypogonadism. Interference in the process of ovulation by endogenous luteinizing hormone fluctuations was eliminated and pregnancies were achieved. The pregnancy rate in the group with polycystic ovary syndrome was 77% per treatment course (six cycles) while that in the group with subnormal progesterone profiles was 61.5%. Patients showing no abnormality achieved no pregnancy, demonstrating the redundancy of interference with normal ovarian function.

Adult↗
PubMed1988

Growth hormone facilitates ovulation induction by gonadotrophins.

The addition of biosynthetic human growth hormone (GH) to treatment with human menopausal gonadotrophin (hMG) significantly augmented the ovarian response in four patients treated for in-vivo and three patients treated for in-vitro fertilization who had previously been resistant to hMG. The amount, duration of treatment and daily effective dose of hMG were all reduced by growth hormone. This action of growth hormone offers a new approach to ovulation induction.

Adult↗
PubMed1975

Ovulation induction during the anovulatory season in Saimiri sciureus.

Captive squirrel monkeys show a seasonal response to a subtle ovulation induction regime of the five days of progesterone, four days FSH (1 mg/day) and a dose of HCG (500 IU), with the minimal response occurring from July to September. A 3 times 3 factorial design with 18 adult female monkeys was used to determine the effects of increasing doses of HCG (500, 1,000, OR 1,500 IU) and increasing dose of duration of FSH (1 mg for four days, 2 mg for four days, or 1 mg for five days) on ovulation between early July and mid-October. An increase in either dose or duration of FSH increased ovulation while increasing HCG was ineffective.

Animals↗
PubMed1996

Successful twin pregnancy in homozygous beta-thalassemia after ovulation induction with growth hormone and gonadotropins.

OBJECTIVE: To describe infertility treatment and pregnancy outcome in a patient with transfusion-dependent beta-thalassemia major and hypopituitarism. DESIGN: Case report. SETTING: University-affiliated infertility clinic. PATIENT: Twenty-four-year-old infertile patient with homozygous beta-thalassemia. INTERVENTION: Co-treatment with GH and gonadotropins. RESULTS: Ovulation induction with clomiphene citrate or gonadotropins alone was unsuccessful. Combined treatment with hMG, hCG, and recombinant human GH followed by intrauterine insemination resulted in a viable twin pregnancy. CONCLUSION: Human GH as an adjunct to hMG and hCG seems to be a sensible approach in the treatment of infertile homozygous beta-thalassemic patients among which very few pregnancies are reported.

Adult↗