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PubMed1996

Ovulation induction, infertility, and ovarian cancer risk.

OBJECTIVE: To review critically the published data regarding the proposed association of ovulation induction, infertility, and an increased risk of ovarian cancer. DESIGN: A medline search was conducted to identify all case reports, epidemiologic studies, and clinical investigations containing data relevant to infertility, treatment of infertility, and the associated risk of ovarian cancer. Additional sources were obtained from reference lists of original research and review articles. Particular emphasis was placed on the most recently published reports examining these associations. RESULTS: Four case-control studies and three retrospective cohort studies, as well as a large meta-analysis of three additional case-control studies were identified as presenting the most pertinent clinical data. CONCLUSION: Currently available data in the literature suggest that an association between ovulation induction and ovarian cancer does not indicate necessarily a causal effect. Infertility alone is an independent risk factor for the development of ovarian cancer. Nulliparous women with refractory infertility may harbor a particularly high risk of ovarian cancer, irrespective of their use of fertility drugs. Furthermore, the apparent association between fertility drug use and ovarian cancer may arise because these women are the most likely to have used ovulation-stimulating agents as part of their infertility treatment. Close clinical surveillance of patients before, during, and after treatment of infertility is warranted.

Female↗
PubMed1989

Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction.

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.

Abortion, Spontaneous↗
PubMed2002

Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction.

The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity. Here we will summarize the data supporting the effect of metformin on improving hyperandrogenaemia and hyperinsulinaemia in PCOS patients. We propose that metformin benefits PCOS patients undergoing gonadotrophin therapy and IVF as well as ovulation induction. We also advocate the use of insulin sensitizing drugs to reduce miscarriage rates, and risks associated with coronary artery disease, gestational diabetes and obesity.

Androgens↗
PubMed1992

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

Animals↗
PubMedDate not supplied

The value of laboratory tests and ultrasonography in evaluating ovarian response to ovulation induction treatment with low-dose recombinant follicle-stimulating hormone.

OBJECTIVE: To compare basal (cycle day 3) follicle-stimulating hormone (FSH) level, clomiphene citrate challenge test (CCCT), gonadotropin-releasing hormone agonist stimulation test (GAST), and mean ovarian volume estimation by ultrasound for predicting the subsequent ovarian response. DESIGN: Prospective, randomized, clinical study. SETTING: Referral university hospital. PATIENTS: One hundred and forty-four women with unexplained infertility undergoing their first ovulation induction treatment with low-dose recombinant FSH. INTERVENTIONS: Patients were randomized into four groups. Basal FSH levels were evaluated in group I (n = 36). Clomiphene citrate challenge test (CCCT) and gonadotropin-releasing hormone agonist stimulation test (GAST) were carried out in group II (n = 36) and group III (n = 36), respectively. Transvaginal ultrasound was performed for ovarian volume measurements in group IV (n = 36). In the subsequent cycle, all women received ovulation induction therapy with recombinant FSH. MAIN OUTCOME MEASURES: Number of mature (> or = 14 mm) follicles and the number of recombinant FSH ampules required for successful ovulation induction. RESULTS: Ovarian volume estimation by transvaginal ultrasound, compared to the other three tests, had the most powerful positive correlation with the number of mature follicles (r = 0.84, P < .0001) and the most powerful negative correlation (r = -0.75, P < .0001) with the amount of recombinant FSH used per cycle. CONCLUSION: Mean ovarian volume estimation by transvaginal ultrasound might be more useful than basal FSH values, CCCT, and GAST for predicting ovarian response to low-dose recombinant FSH treatment.

Clomiphene↗
PubMed2004

An economic comparison of a laparoscopic electrocautery strategy and ovulation induction with recombinant FSH in women with clomiphene citrate-resistant polycystic ovary syndrome.

BACKGROUND: Recombinant FSH (rFSH) is the current standard treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) that do not respond to clomiphene citrate. Ovulation induction with rFSH is known to be costly due to the necessity of daily injections and intensive monitoring. An alternative strategy, starting with electrocautery of the ovaries, may be a less costly option. METHODS: An economic evaluation was set up alongside a multicentre randomized clinical trial comparing laparoscopic electrocautery of the ovaries, followed by clomiphene citrate and rFSH when anovulation persisted, and treatment with rFSH in 168 women with clomiphene citrate-resistant PCOS. Data on resources used for treatment and productivity loss were collected prospectively up to an eventual ongoing pregnancy with a time horizon of 12 months. RESULTS: At 12 months the ongoing pregnancy rates were 67% for both the electrocautery strategy and rFSH treatment. Mean total costs per woman were 5308 euros for the electrocautery strategy and 5925 euros for treatment with rFSH, resulting in a mean difference of 617 (95% CI: -382 euros to 1614 euros). CONCLUSIONS: The total treatment costs up to an ongoing pregnancy are comparable for rFSH treatment and an alternative strategy starting with electrocautery. Due to a lower number of multiple pregnancies, the electrocautery strategy can be expected to result in lower total costs when costs of the delivery are included.

Adult↗
PubMed1988

LHRH analogues for ovulation induction, with particular reference to polycystic ovary syndrome.

Infertile women with PCO have been treated with exogenous gonadotrophins (hMG/hCG) for ovulation induction either with or without LHRH-agonist treatment. Those treated without LHRH-agonist-induced LH suppression showed PL in greater than 30% of the cycles and this problem was eliminated by LHRH-agonist therapy. The pregnancy rate (approximately 80% of patients) during the combined therapy was approximately twice that of the group treated with hMG/hCG alone. The suppression of endogenous LH by the LHRH-agonist appeared to have no effect upon the profiles of follicular development in response to hMG, and a high rate of follicle recruitment characterized all PCO treatment cycles irrespective of circulating LH concentrations. These results suggest that LH suppression improves the efficacy of ovulation induction but has no influence on the primary metabolic disturbance in the PCO syndrome.

Drug Therapy, Combination↗
PubMedDate not supplied

Ovarian cancer associated with ovulation induction: a case report.

A case report of a 38 year old lady who developed ovarian malignancy following 3 cycles of ovulation induction therapy is presented. She was observed to have clinically normal ovaries at laparotomy for tubal infertility 12 months previously. Although direct causal link between ovarian stimulation and cancer has not been established yet, a case is made for increased monitoring of patients receiving ovulation induction medication by physicians.

Adenocarcinoma↗
PubMed1996

Different gonadotropin and leuprorelin ovulation induction regimens markedly affect follicular fluid hormone levels and folliculogenesis.

OBJECTIVES: To clarify the endocrine mechanisms underlying the outcome of different ovulation induction regimens with gonadotropins and GnRH agonists (GnRH-a). DESIGN: Prospective study. SETTING: Reproductive Endocrinology Center, University of Bologna. PATIENTS: Forty eumenorrheic women randomly assigned to four groups of 10 subjects each. INTERVENTIONS: Ovulation induction regimens: group A, purified FSH only; group B, purified FSH and flare-up GnRH-a; group C, purified FSH and long GnRH-a; and group D, hMG and long GnRH-a. MAIN OUTCOME MEASURES: Pelvic ultrasound and hormone levels in daily serum samples and in follicular fluid drawn immediately before hCG administration. RESULTS: Exogenous gonadotropin dose did not differ among groups. Group B had fewer preovulatory follicles than group C. Group B had higher serum LH, FSH, E2, P, T, and follicular fluid LH, E2, T, and alpha-inhibin than groups C and/or D. Groups C and D did not differ. CONCLUSIONS: Long GnRH-a regimens improved follicle yield and the endocrine milieu in spite of comparable exogenous gonadotropin dose and lower serum FSH and thus appear to be preferable in assisted reproduction. Reduced folliculogenesis found in flare-up GnRH-a regimens could be mediated by the atretic effects of high intraovarian androgens. Efficacy of purified FSH and hMG was comparable.

Adult↗
PubMedDate not supplied

The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction.

LH plays critical roles in the control of folliculogenesis and ovarian function in humans. LH activity administration during gonadotrophin ovulation induction can enhance ovarian response and optimise treatment. More specifically, LH activity (both LH and low-dose hCG) can support the growth and stimulate the maturation of larger ovarian follicles as a result of specific granulosa cell receptors that develop after a few days of FSH priming. This action of LH is independent of FSH, and it has been shown recently that the last stages of follicular development can be supported by sole administration of LH activity in the form of low-dose hCG, without causing premature luteinization. Reproductively competent oocytes and pregnancy can be obtained with this regimen. Furthermore, LH activity is capable of reducing the development of small ovarian follicles (<10 mm) that may predispose patients to developing complications such as the ovarian hyperstimulation syndrome. Thus, better understanding of the dynamics and mechanisms that control human folliculogenesis and a more rational and selective use of LH activity administration may allow a reduction in cost and increased safety, while maintaining a high efficacy of the ovulation induction regimens used in assisted reproduction.

Chorionic Gonadotropin↗
PubMed1982

[A new method of ovulation induction with HMG-HCG by a E2 rapid radioimmunoassay (author's transl)].

We schemed out a new method of ovulation induction with HMG-HCG using E2 rapid radio-immunoassay (RIA). On measurement of E2 values, the method of E2-(125)I kit (Daiichi Radioisotope Labs., LTD) was simplified, that is, an omission of defatting, shortened incubation time and a standard curve constructed by three points. There was a good correlation between the E2-(125)I kit method and the E2 rapid RIA method in E2 values obtained. The lowest detectable amount was 75 pg/ml. This rapid method seemed to be suitable to monitor the extent of follicular maturation during HMG therapy. Our new method of ovulation induction was as follows. (i) On the basis of E2 values measured every 3 days, HMG dosage was adjusted. (ii) When E2 was over 400 pg/ml for 2 days, HCG was given on the next day. with this method, there was an increase in the percentage of ovulatory cycles from 54.5% to 100% and a decline in the incidence of ovarian enlargement and the ascites. This new method minimized inconvenience and expense of E2 determination without drastically influencing therapy outcome.

Adult↗
PubMed1989

Effects of previous ovarian surgery on the follicular response to ovulation induction in an in vitro fertilization program.

This study examined the effects of previous ovarian surgery on the clinical response to ovulation induction with clomiphene citrate-human menopausal gonadotropin in an in vitro fertilization program. Patients were divided into five clinical groups: group A (n = 63), no previous ovarian surgery; B (n = 9), unilateral cystectomy; C (n = 6), unilateral oophorectomy with no contralateral ovarian surgery; D (n = 7), bilateral ovarian surgery with both ovaries present; and E (n = 4), unilateral oophorectomy and contralateral cystectomy. Patients in group E demonstrated significantly lower serum estradiol on cycle days 9-11 (P less than or equal to .05) and fewer follicles on cycle days 11-12 (P less than or equal to .05) than did patients in groups A-D. The percentage of cancelled cycles increased with increasing amounts of ovarian surgery (P less than or equal to .03). The study suggests that one cause of a poor response to ovulation induction for in vitro fertilization may be prior extensive ovarian surgery.

Adult↗
PubMed1982

Determination of pathophysiological mechanisms in subjects with amenorrhoea and their value in predicting ovulation induction therapy.

A scheme of investigation to determine the pathophysiological mechanisms in 142 women with amenorrhoea is described together with the results of a selective ovulation induction programme. Initial screening tests were performed to identify patients with conditions which were unlikely to respond to any form of treatment (e.g. primary ovarian failure) or in whom other well defined absolute causes of infertility were present. The site of defect within the hypothalamic-pituitary-ovarian axis was then determined by a series of dynamic test procedures. On the basis of these results ovulation induction treatment was selected and given for six treatment cycles. Ovulation was induced in 89.2% of 556 treatment cycles and 60.2% of 125 patients treated for up to six cycles conceived. The rationale and benefits of such an investigative protocol are discussed.

Amenorrhea↗
PubMed1993

Ultrasonically guided follicular aspiration during a pregnancy with massive ovarian cysts following ovulation induction by gonadotropins.

In this report, the treatment by follicular aspiration was evaluated in a pregnant patient with severe ovarian cysts subsequent to ovulation induction with CC and gonadotropins. The patient had dramatic and immediate improvement of the symptoms and general condition as well as a significant shorter hospital stay. The procedure was, under meticulous US guidance, safe and effective, providing additional improvement or increased therapeutic confidence in the severe complications after ovulation induction, as an assisted option during pregnancy.

Adult↗
PubMed2005

Estimating live birth rates after ovulation induction in polycystic ovary syndrome: sample size calculations for the pregnancy in polycystic ovary syndrome trial.

Polycystic ovary syndrome (PCOS) affects approximately 5% of the female population, and is a leading cause of infertility, primarily secondary to anovulation. Clomiphene citrate has been standard therapy for ovulation induction in patients seeking pregnancy, but recent evidence suggests that insulin sensitizing agents such as metformin may also be effective. The National Institute of Child Health and Human Development's Reproductive Medicine Network has begun a randomized, double-blind trial of clomiphene vs. metformin vs. clomiphene plus metformin for the induction of ovulation in patients with PCOS seeking pregnancy, with live birth rate as the primary outcome. Because the available literature was largely limited to surrogate outcomes such as ovulation and pregnancy rates, we created a Markov model to derive estimates of likely live birth rates in each arm. Using these estimates, we then constructed an algorithm that allowed only two formal comparisons between the three arms. First, we assumed that combination therapy would have to be superior to the next best single-agent therapy in order to be preferred, because of complexity, costs, increased side effects, etc. If combination therapy is not superior to the next best single agent, then the only other comparison of interest is between the two single agent therapies. Because the third possible comparison, between the best and worst of the three therapies, is not clinically relevant, it can be eliminated from formal statistical consideration, with subsequent reduction in sample size. Based on the opinion of the Network Steering Committee that a 15% absolute difference in live birth rates would be clinically relevant, our methodology resulted in a sample size of 226 per arm, or a total of 678 subjects. The PPCOS trial should definitively answer the question of the relative efficacy of metformin, clomiphene, and combination therapy in the treatment of infertile women with PCOS.

Adolescent↗
PubMed1998

[Experimental study on the role of insulin-like growth factor-I in ovulation induction].

OBJECTIVE: To investigate the possibility of insulin-like growth factor-I (IGF-I) as an adjunctive factor for ovulation induction. METHODS: The model of anovulatory mice was established by single injection of testosterone propionate. Thirty anovulatory mice were divided into 3 groups, each contained 10 mice. IGF-I 1 microgram + human menopausal gonadotropin (hMG) 5 IU, IGF-I 2 micrograms or hMG 10 IU alone was injected intraperitoneally to each group respectively. Cyclic changes of vaginal smear and numbers of oocytes in fallopian tubes were used to assess the effect. RESULTS: Vaginal smears of 8 mice in IGF-I + hMG group, 6 mice in hMG group and 2 mice in IGF-I group returned to normal cyclic pattern. The differences between IGF-I + hMG group and IGF-I or hMG groups were significant (P < 0.01 and P < 0.05), but the difference between IGF-I group and hMG group was not significant (P > 0.05). The average numbers of oocytes within fallopian tubes were 12.3 in IGF-I + hMG group and 9.2 in hMG group (P < 0.05). In IGF-I group there were no oocytes in the fallopian tubes of two mice whose vaginal smears returned to normal. CONCLUSION: IGF-I may be a potential agonist agent for ovulation induction.

Animals↗