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PubMed1988

Vaginal progesterone administration before ovulation induction with exogenous gonadotropins in polycystic ovarian syndrome.

We studied the value of vaginal progesterone (P4) in suppressing serum LH concentrations and restoring normal luteal phase serum LH concentrations before administration of exogenous gonadotropins in anovulatory women with the polycystic ovarian syndrome (PCOS). P4 (50 mg every 12 h) was administered by vaginal suppository to 9 women (18 cycles) for 14 days before ovulation induction with human menopausal gonadotropin (hMG) and hCG. Serum LH, FSH, estradiol, P4, and PRL levels were measured daily. A biphasic effect on LH secretion occurred during P4 administration. Peak serum LH levels occurred on day 5 (125% of basal levels; P less than 0.05) of vaginal P4 suppository use, followed by a progressive fall (P less than 0.05) to 79% of basal levels, but serum LH levels were still higher than those in normal women despite achieving physiological luteal phase P4 concentrations. Ovulation occurred in 56% of cycles after P4 and hMG/hCG treatment and in 65% of control cycles after hMG/hCG alone. In 7 women, serum LH was measured at 10-min intervals for 6 h before and after vaginal P4 administration for 10 days. LH pulse frequency decreased from 7.4 +/- 1.1 to 4.4 +/- 1.2 pulses/6 h (P less than 0.01), and LH pulse amplitude increased from 3.8 +/- 1.8 to 6.1 +/- 2.9 IU/L (P less than 0.01) after P4 administration. We conclude that vaginal P4 (50 mg every 12 h) 1) produces serum P4 concentrations within the normal range for the luteal phase of the menstrual cycle; 2) elevates serum LH, but not FSH, within 5 days; 3) decreases LH pulse frequency and increases LH pulse amplitude after 10 days, but does not normalize serum LH values; and 5) fails to improve the results of subsequent ovulation induction with exogenous gonadotropins in patients with PCOS.

Administration, Intravaginal↗
PubMed1997

Effect of disruption versus continuation of gonadotrophin-releasing agonist after human chorionic gonadotrophin administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization.

Previous studies have described the luteolytic effect of gonadotrophin-releasing hormone agonist (GnRHa) administered in the early luteal phase. The present work was undertaken to compare in a prospective and randomized design the effect of disruption versus continuation of daily GnRHa after human chorionic gonadotrophin (HCG) administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization (IVF). Two different studies were designed and a total of 38 ovum donors, aged 23-30 years, were included. In the first study, the effect of GnRHa on the early luteal phase of IVF-stimulated cycles was investigated (n = 27); the patients were divided into two groups, according to whether they stopped (n = 13) or continued with daily GnRHa injections (n = 14) for an additional period of 15 days after HCG administration. Blood was drawn from luteal phase days 2 to 6 (day 0 = day of HCG administration) and oestradiol and progesterone concentrations were analysed. The second study focused on the effects of continuation versus disruption of GnRHa administration in the mid-late luteal phase. A similar design was employed including six patients who stopped GnRH on day 0 and five other women who continued GnRHa for 15 days after HCG administration. In this second study, blood was drawn from days 5 to 11 and oestradiol, progesterone and luteinizing hormone (LH) concentrations were analysed. IVF parameters were similar in both groups. The results indicate that continuous GnRHa administration, after HCG injection, does not produce changes in oestradiol, progesterone and LH concentrations in the early, mid- and late luteal phases compared to those patients in whom GnRHa is discontinued at the day of HCG administration. The present work demonstrates that, when ovulation induction is performed, the corpus luteum is driven primarily by the HCG, regardless of the administration or disruption of GnRHa in the luteal phase. This suggests that the lack of differences between continuation versus disruption of GnRHa may be due to the accumulation of the product over the previous 2-3 weeks of treatment.

Adult↗
PubMed2001

[Effects of ovulation induction on expression of integrins alpha 4 beta 1 in endometrium].

OBJECTIVE: To study the effect of clomiphene citrate (CC) and human menopausal gonadotropin (hMG) on the expression of integrins alpha 4 beta 1 during implantation window in endometrium. METHODS: Endometrium integrin alpha 4 beta 1 expression was detected by immunohistochemistry method in the mid-secretory phase of 48 normal natural cycles. CC + hCG or CC + hMG + hCG cycles in 30 polycystic ovary syndrome (PCOS) patients and 48 normal women. RESULTS: The expression of endometrial integrin alpha 4 beta 1 was stronger in the natural cycles than those of ovulation induction cycles with CC + hCG or CC + hMG + hCG. So was the pregnancy cycles as compared with the non-pregnant cycles. CONCLUSION: The endometrial receptivity in the min luteal phase and pregnant rate declined during ovulation induction by CC + hCG or CC + hMG + hCG in either normal women or PCOS patients.

Adult↗
PubMed1995

Cotreatment with growth hormone and gonadotropin for ovulation induction in hypogonadotropic patients: a prospective, randomized, placebo-controlled, dose-response study. European and Australian Multicenter Study.

OBJECTIVE: To explore the dose-response relationship of cotreatment with GH in the augmentation of the ovarian response to stimulation by gonadotropins. DESIGN: Patients were randomly allocated to receive hMG and GH (4, 12, 24 IU) or hMG and placebo on alternate days for up to seven injections. PATIENTS: Sixty-four women with hypogonadotropic hypogonadism in eight centers in Europe and one in Australia. MAIN OUTCOME MEASURES: Gonadotropin dosage as a function of GH dose. RESULTS: The mean total number of ampules of hMG (75 IU FSH/ampule) required was 37.2, 30.0, 25.6, and 22.3, respectively. There was also a significant dose-response relationship observed for the duration of gonadotropin therapy and final daily effective dose required. Serum insulin-like growth factor I concentrations increased as a function of GH dose. No significant difference in E2 concentrations, number of large follicles, or cancellation rate was noted between the four groups. There were significantly more pregnancies in the placebo groups compared with the GH groups. Nine adverse reactions were noted, one in the placebo and eight in the GH groups (1 in the 4-IU group, 5 in the 12-IU group, and 2 in the 24-IU group). CONCLUSIONS: We conclude that addition of GH to gonadotropin treatment exhibits a dose-related amplification of gonadotropin action on the ovary and reduction of gonadotropin dosage required to achieve ovulation induction. The study did not however define the minimum effective dose of GH for gonadotropin-stimulated ovulation induction.

Adult↗
PubMed2001

Clinical review 126: Roles and novel regimens of luteinizing hormone and follicle-stimulating hormone in ovulation induction.

Although FSH is universally recognized as the key driver of ovarian follicle growth and maturation, the role of LH in these processes is more controversial. LH acts on theca cells to induce androgen substrate for estrogen conversion by the aromatase system; furthermore, LH can affect granulosa cell function starting in the mid- follicular phase, when these cells express LH receptors. The capacity of LH to stimulate granulosa cells in larger follicles (>10 mm diameter) may be the critical mechanism involved in the selection of the dominant follicle in the normal menstrual cycle. Furthermore, the addition of LH activity can shorten and optimize FSH ovulation induction and reduce the development of smaller preovulatory ovarian follicles that are associated with the severe complications of this procedure. Novel mixed gonadotropin administration regimens that incorporate graded amounts of LH and FSH activity may improve efficacy, safety, and cost of ovulation induction, particularly in the area of assisted reproduction.

Endocrine Glands↗
PubMed1988

Programmed ovulation induction and oocyte retrieval for in vitro fertilization.

Forty-two patients underwent programmed ovulation induction for oocyte retrieval. They were treated in the preceding cycles with a progestagen, ethynodiol diacetate, at a dose of 2 mg twice daily. Two groups were defined based upon the stimulation protocol: Group A1 was stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), and Group A2 with follicle-stimulating hormone (FSH) and hMG. They were compared to two randomized control groups of patients who received the same induction but were classically monitored. There was a high proportion of spontaneous ovulations in the programmed group (8/42) compared to the nonprogrammed group (0/42). There was a nonsignificant difference in the number of oocytes obtained or embryos replaced per cycle. Four pregnancies were obtained in the programmed group (24% per transfer), against 10 in the nonprogrammed patients (32% per transfer). The results of this method seem to be better using FSH for ovulation stimulation and a verification of the serum estradiol on the day of induction with human chorionic gonadotropin (hCG) and the following day (semiprogrammed method).

Adult↗
PubMed2004

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. OBJECTIVES: To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. MAIN RESULTS: Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Female↗
PubMed1987

Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. I. Safety and effectiveness with outpatient therapy.

Pulsatile intravenous gonadotropin-releasing hormone (IV-GnRH) was used in 36 infertile patients with primary amenorrhea (n = 5), secondary amenorrhea due to hypothalamic chronic anovulation (HCA) (n = 22), hyperprolactinemia (n = 1) or polycystic ovary syndrome (PCOS) (n = 5), and oligomenorrhea (n = 3). Treatment was commonly initiated in the hospital but was then continued outside, with patients and local physicians accepting responsibility for maintaining IV-GnRH delivery systems. Twenty-eight of 113 treatment cycles (24.8%) resulted in pregnancy, with four spontaneous abortions (14.3%) and four twin pregnancies (16.7%) among 24 births. Probability of pregnancy per treatment cycle was significantly higher for primary amenorrhea (0.30) and for HCA (0.33) than for PCOS (0.07; P less than 0.05) and for oligomenorrhea (no conceptions; P = 0.01). Ovulatory cycles were not achieved in five patients (primary amenorrhea, n = 1; PCOS, n = 3; oligomenorrhea, n = 1). There were no serious complications; six patients recorded eight febrile episodes, which responded quickly to antibiotic therapy and cannula change. The authors conclude that outpatient IV-GnRH is safe, practical, and effective for follicular stimulation and ovulation induction in women presumed to have GnRH deficiency and in whom clomiphene therapy fails, and that less intensive monitoring is needed compared with gonadotropin ovulation induction therapy.

Adult↗
PubMed2003

A case of lupus peritonitis and cystitis after ovulation induction therapy.

We report a patient in whom lupus peritonitis and cystitis developed after ovulation induction therapy with human menopausal and chorionic gonadotropins followed by in vitro fertilization and embryo transfer. The lupus peritonitis and cystitis presented clinically as an acute abdomen. This disease should not be misdiagnosed as a nonspecific or infectious pelvic peritonitis, especially after oocyte retrieval.

Adult↗
PubMed1998

Gonadotropin ovulation induction and pregnancies in women with Kallmann's syndrome.

Only 17 cases of pregnancy in women with Kallmann's syndrome have been reported in the literature, eight as case reports. In our clinic, we diagnosed seven women with complete Kallmann's syndrome in a 16-year period. In five cases (unprimed patients) the diagnosis was established for the first time, while in the other two cases diagnosis had been established earlier. The five unprimed patients received hormone therapy (HRT) immediately after diagnosis. The other two patients had already been on HRT. Four patients wanted to bear children. Follicular evolution and maturation was induced with daily human menopausal gonadotropin (hMG) administration. The results were monitored through plasma estradiol (E2) determinations and ultrasonography. Ovulation was induced with hCG administration. Five pregnancies were achieved in three patients, resulting in four healthy neonates. Two women achieved a second pregnancy. Nausea and vomiting did not occur in any of our five pregnancies. We found no significant differences between the total hMG dose needed for ovulation induction, the number of stimulation days, estradiol plasma concentrations and the number of follicles with diameter > or = 17 mm, in either conceptional or non-conceptional cycles. In fact, the total hMG dose administered was lower and the days of stimulation were significantly fewer in women on their second pregnancy. There was no difference in plasma estradiol concentrations and the number of follicles with diameter > or = 17 mm. In conclusion, ovulation induction and pregnancy in women with complete Kallmann's syndrome is not such a difficult procedure as was believed in the past. A previous pregnancy seemed to augment ovarian sensitivity to gonadotropins.

Adult↗
PubMed2005

Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment.

OBJECTIVE: To assess whether the addition of metformin to gonadotrophin ovulation induction in insulin-resistant, normogonadotrophic, anovulatory women alters ovarian responsiveness to exogenous FSH. DESIGN: Placebo-controlled double-blind assessment in an academic hospital. RESULTS: After a progestagen withdrawal bleeding, patients were randomised for either metformin (n = 11) or placebo (n = 9) treatment. In cases of absent ovulation, exogenous FSH was subsequently administered to induce ovulation. Only during metformin treatment did body mass index and androgen (androstenedione and testosterone) levels decrease, whereas FSH and LH levels increased significantly. In the metformin group, a single patient ovulated before the initiation of exogenous FSH. Significantly more monofollicular cycles and lower preovulatory oestradiol concentrations were observed in women receiving FSH with metformin compared with FSH alone. CONCLUSIONS: Metformin co-treatment in a group of insulin-resistant, normogonadotrophic, anovulatory patients resulted in normalization of the endocrine profile and facilitated monofollicular development during the FSH induction of ovulation.

Adolescent↗
PubMed1984

Ovulation induction with subcutaneous pulsatile gonadotropin-releasing hormone: the role of supplemental human chorionic gonadotropin in the luteal phase.

Four subjects with hypothalamic amenorrhea were administered subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction. GnRH was discontinued at the time of presumed ovulation in all cases. In the first two patients the luteal phase was supported with human chorionic gonadotropin in the initial cycle but not in the second cycle. In patient 3, the reverse was true. Patient 4 had only one cycle on GnRH, and it was unsupported. Daily blood samples were obtained for luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone (P); and frequent pelvic ultrasound examinations were performed. Presumed ovulation as determined by ultrasound occurred in all seven cycles. The first three patients had short luteal phases with poor P production in the unsupported cycles. However, the fourth patient, who had shown pituitary response in GnRH testing, had a normal luteal phase with good P production without human chorionic gonadotropin support. These data support the notion that subcutaneous pulsatile GnRH can be used for the induction of ovulation. However, if the luteal phase is not supported, an inadequate corpus luteum may result.

Amenorrhea↗
PubMed2000

Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: During ovulation induction (OI), ovarian stimulation is accomplished by hormonal manipulation, which includes administration of gonadotropins, gonadotropin-releasing hormone agonists, follicle-stimulating hormone, and luteinizing hormone. In in vitro fertilization (IVF), progesterone is often added. Because of the possibility of hormone-associated flare or thrombosis, patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (primary APS) undergoing OI/IVF are potentially at increased risk. The present study was conducted in order to assess this risk. METHODS: Nineteen women who underwent 68 cycles of OI/IVF were studied by interview and retrospective chart review. RESULTS: Four OI/IVF cycles (25%) in SLE patients resulted in increased lupus activity and 2 (13%) in ovarian hyperstimulation syndrome. One patient with primary APS who was given heparin during multiple cycles developed osteopenia. No thrombosis occurred. Pregnancy complications included toxemia, lupus flare, gastrointestinal hemorrhage due to Mallory-Weiss tear, polygestation, and diabetes. Postpartum complications included nephritis flare, costochondritis, and suicidal depression. Lupus flares occurred at expected rates. Five of 16 cycles (31%) in 7 SLE patients, 5 of 48 cycles (10%) in 10 primary APS patients, and 0 of 5 cycles in 2 women with antiphospholipid antibody (without SLE or primary APS) resulted in liveborn children, including multiple gestations (3 twin sets with 4 surviving infants and 2 triplet sets with 3 surviving infants). Seven of 14 living children (50%) were premature, 3 had neonatal lupus, and 1 had pulmonic stenosis. Five surviving infants (38%) had complications unrelated to prematurity. CONCLUSION: Although OI/IVF can be successful in SLE and primary APS patients, rates of fetal and maternal complications are high.

Adult↗
PubMed1987

[Endocrinological background of pituitary desensitization during pulsatile LH-RH therapy for ovulation induction in amenorrheic women].

In order to elucidate the endocrinological background of patients in whom ovulation induction by pulsatile LH-RH administration resulted in failure, 16 women with hypothalamic amenorrhea were treated with 10 to 20 micrograms of LH-RH injected subcutaneously every 2 hrs. Six women did not ovulate, and 5 of them showed pituitary desensitization since the basal gonadotropin concentration gradually decreased and the response to LH-RH test (100 micrograms i.v.) became blunted by the treatment. No significant differences between the ovulated and desensitized groups were seen in basal LH, FSH, E2, PRL levels, LH/FSH ratio and response to LH-RH test performed prior to the treatment. In addition, the plasma LH-RH profile after subcutaneous injection of 10 micrograms of LH-RH was highly pulsatile in both groups. However, in the desensitized group, all were obese, showed impaired GH response to both insulin tolerance and GH-RH tests, and had episodic LH secretion with higher frequency compared to the ovulated group. These results suggest that the desensitized women had occult pituitary dysfunction and hypersecretion of endogenous LH-RH which stimulated the pituitary close to the level of desensitization. The mechanism of hypersecretion of endogenous LH-RH is discussed.

Adult↗
PubMed2000

Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations.

GnRH receptor mutations have recently been identified in a small number of familial cases of nonanosmic hypogonadotropic hypogonadism. In the present report we studied a kindred in which two sisters with primary amenorrhea were affected with GnRH deficiency due to a compound heterozygote mutation (Gln(106)Arg, Arg(262)Gln) and performed extensive phenotyping studies. Baseline patterns of gonadotropin secretion and gonadotropin responsiveness to exogenous pulsatile GnRH were examined in the proband. Low amplitude pulses of both LH and free alpha-subunit (FAS) were detected during 24 h of every 10 min blood sampling. The proband then received exogenous pulsatile GnRH i.v. for ovulation induction, and daily blood samples for gonadotropins and sex steroids were monitored. At the conventional GnRH replacement dose for women with hypogonadotropic hypogonadism (75 ng/kg), no follicular development occurred. At a GnRH dose of 100 ng/kg, the level and pattern of gonadotropin secretion more closely mimicked the follicular phase of normal women; a single dominant follicle was recruited, and an endogenous LH surge was elicited. However, the luteal phase was inadequate, as assessed by progesterone levels. At a GnRH dose of 250 ng/kg, the gonadotropin and sex steroid dynamics reproduced those of normal ovulatory women in both the follicular and luteal phases, and the proband conceived. The FAS responses to both conventional and high dose GnRH were within the normal range. The following conclusions were made: 1) Increased doses of GnRH may be used effectively for ovulation induction in some patients with GnRH receptor mutations. 2) Higher doses of GnRH are required for normal luteal phase dynamics than for normal follicular phase function. 3) Hypersecretion of FAS in response to exogenous GnRH, which is a feature of congenital hypogonadotropic hypogonadism, was not seen in this patient with a GnRH receptor mutation.

Adolescent↗
PubMed2004

Ovulation induction and successful pregnancy outcome in two patients with Prop1 gene mutations.

OBJECTIVE: To describe ovulation induction and pregnancy outcome in a unique model of genetically determined combined pituitary hormone deficiency (CPHD), with respect to the necessity for GH substitution therapy. DESIGN: Case report. SETTING: Academic units. PATIENT(S): Two patients with childhood onset of CPHD (GH, PRL, TSH, LH, FSH) caused by a genetic defect (GA296del mutation) of the Prop1 gene. MAIN OUTCOME MEASURE(S): Ovulation, pregnancy outcome, and fetal growth. RESULT(S): Successful pregnancy outcome and delivery of normal, full-term newborns were achieved in both patients with the use of gonadotropins and L-T(4). Growth hormone supplementation was not necessary. No lactation was observed. CONCLUSION(S): Patients with Prop1 gene mutations constitute a unique model for studying the role of GH and PRL in ovulation, pregnancy, and fetal growth. Our data indicate that for women with CPHD, ovulation and pregnancy are possible with a classic regimen for hypogonadotropic hypogonadism, without the need for GH substitution therapy.

Adolescent↗
PubMed1991

Can ultrasonography reliably predict the occurrence of multiple pregnancies in gonadotrophin ovulation induction?

A retrospective study of 78 patients with 106 stimulated conception cycles after successful gonadotrophin ovulation induction was made to analyze the relationship between the sizes and numbers of ovarian follicles seen on ultrasound and the eventual number of conceptions that resulted in each cycle. Fifteen cycles (14.2%) resulted in spontaneous abortions. There were 58 singleton pregnancies (54.8%), 26 sets of twins (24.5%), 6 sets of triplets (5.6%) and 1 set of quadruplets (0.9%). In 86 cycles with the last scans performed shortly before the ovulating dose of HCG, 3 or more mature follicles were found in 50 (58%). These cycles resulted in 31 (62%) singletons, 16 (32%) twin pregnancies and 3 (6%) triplet pregnancies. Pregnancies resulted even when there were no 'mature' follicles seen on scan. No statistical correlation was found between plurality of pregnancy and size or number of follicles, or oestradiol excretion on the day the ovulating dose of HCG was given, although high-order multiple pregnancies were more likely if the oestrogen excretion was more than 200 ug/24 hours (p = 0.001). The dosage of HCG correlated inversely with the occurrence of multiple pregnancies (p = 0.02). In conclusion, neither oestrogens nor ultrasonography could accurately predict multiple conceptions in gonadotrophin stimulated cycles.

Estrogens↗