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PubMed1990

Methods of ovulation induction.

The results of ovulation induction in patients with ovulatory dysfunction were reviewed for a one year period. Eighty-six women were assigned to four groups: secondary amenorrhea, anovulation, oligo-ovulation, and luteal phase defect/short luteal phase (LPD). All patients were monitored with basal body temperature (BBT) graph, postcoital testing, and ultrasonic scanning of ovarian follicles. All patients received therapy with clomiphene citrate (CC) for a minimum of four cycles and 13 patients conceived. Fifty patients were offered additional therapy with human menopausal gonadotropins (HMG-HCG). Seventeen completed a minimum of four cycles, and 13 conceived. The number of CC-treated patients with poor mucus quality in the face of adequate follicular development was 24, or 48%. The overwhelming problem with ovulation induction when CC failed was the large number of patients who dropped out of therapy, 48%. In summary, close monitoring during ovulation induction to confirm ovulation, and assess mucus quality and luteal function allow detection and correction of inadequate response. Induction of ovulation can be highly successful if patients can follow through and complete protocols of therapy.

Adult↗
PubMed2004

Aromatase inhibitors in ovulation induction.

The new third generation aromatase inhibitors are extremely potent and specific oral inhibitors of estrogen production. We reported the success of using aromatase inhibitors for induction of ovulation in World Health Organization (WHO) type II anovulatory patients. Promising pregnancy rates were associated with the use of aromatase inhibitors for induction of ovulation in these women. In addition, the use of aromatase inhibition in conjunction with gonadotropin injection was associated with a significant reduction in the gonadotropin dose required for optimum controlled ovarian hyperstimulation. We believe that these oral agents are efficient and safe and have many advantages compared with clomiphene citrate (CC). We propose that aromatase inhibitors will replace CC in the future as the new primary treatment for ovulation induction. In this review, we present an update on the use of aromatase inhibitors for induction of ovulation and we discuss several new areas of potential interest regarding the use of aromatase inhibitors, either alone or together with recombinant follicle-stimulating hormone (FSH) for infertility treatment. Further research in these areas may demonstrate an expanded role in assisted reproductive technologies.

Anovulation↗
PubMed2006

Role of aromatase inhibitor in ovulation induction in patients with poor response to clomiphene citrate.

AIM: To examine the efficacy of aromatase inhibitor in the induction of ovulation. METHODS: This prospective clinical trial in patients with infertility and poor response to clomiphene citrate (CC) was undertaken in a tertiary referral infertility clinic. Thirty-five infertile patients, who were treated by clomiphene citrate for several cycles and referred to the infertility clinic, were the target population. Initially, the response of CC was assessed by same dose of CC that the patient had in her last cycle. The patients who did not respond adequately were treated by aromatase inhibitor 2.5-5 mg/day from day 3-7 of the menstrual cycle. The main outcome measures were the number of mature follicles, ovulation rate, endometrial thickness and pregnancy rate. RESULTS: Twenty-seven (90%) patients developed mature follicles by day 12. The majority (77.77%) developed single follicle. Except for one cycle of one patient, the follicles of all patients were ruptured in all cycles and seven (25.94%) got pregnant. CONCLUSION: The aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility in patients that failed to ovulate by CC.

Adult↗
PubMed2003

Is there a future for ovulation induction in the current era of assisted reproduction?

The clinical use of medical induction of ovulation in normogonadotrophic anovulatory women (WHO II), including polycystic ovary syndrome, is increasingly questioned. However, we believe that this treatment modality still represents a highly effective means of fertility treatment in women with low pregnancy chances without intervention. A conventional treatment algorithm involving clomiphene citrate (CC) followed by FSH induction of ovulation may result in a 71% cumulative singleton live birth rate. In attempts to improve treatment outcome further and reduce complication rates, new compounds such as insulin-sensitizing agents or aromatase inhibitors are currently used increasingly. Approaches such as patient selection for different treatment modalities on the basis of initial screening characteristics and alternative protocols for FSH ovulation induction may also be proposed to render treatment algorithms more patient tailored and therefore improve overall outcomes. More research is needed in this area, rather than referring these patients to assisted reproduction prematurely. This may lead to a more individually tailored approach for ovulation induction in a given patient, resulting in a further improvement of the balance between chances for success versus complications.

Clomiphene↗
PubMed1998

Endocrine methods of ovulation induction.

The rationale of ovulation induction is to achieve the development of a single follicle and ultimately a singleton healthy baby. Problems faced by women with anovulatory polycystic ovary syndrome are the sensitivity of the ovary to stimulation and health issues such as obesity. This chapter will discuss medical management including strategies to lose weight, address hyperinsulinaemia with insulin-sensitizing agents, such as metformin, and outline methods of ovulation induction from the usual first-line therapy of clomiphene citrate and the subsequent use of gonadotrophin therapy in clomiphene-resistant patients. Appropriately directed surgical ovulation induction with laparoscopic ovarian diathermy appears to be as efficacious as gonadotrophin therapy but will not be discussed in the context of this chapter.

Adult↗
PubMed1994

[Laparoscopic image of sexual organs in women after ovulation induction].

The assessment was performed of laparoscopic images of the sex organ in 58 women after induction of ovulation. Abnormalities were found in 29 women with permanent lack of ovulation and in six women with achieved ovulation. The changes in the oviducts predominated with an astonishingly low per cent of incidence of endometriosis (5) which probably was not a clinical problem in non-effective ovulation induction. The decision of laparoscopy should be considered also in the cases in which HSG performed earlier gave positive results.

Animals↗
PubMed1990

Alternate regimens for ovulation induction in polycystic ovarian disease.

The patient with PCOD remains a challenge to the reproductive endocrinologist. Although successful induction of ovulation can often be achieved using standard therapeutic regimens of CC or hMG, too often this group of anovulatory patients fails to respond as expected. Over the past 10 to 15 years, alternate approaches to ovulation induction have been investigated with encouraging results. Whereas no one method is productive in all patients, these varied regimens offer us a number of options in dealing with this difficult clinical problem.

Clomiphene↗
PubMed2004

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction.

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.

Adult↗
PubMed2000

[Ovulation induction and the risk of ovarian tumors].

In the last years it has been observed a more and more increasing number of women submitted to therapies for induction of ovulation (disorders of the ovulation represent 33% of the causes of female infertility). In 1998, these therapies had been administrated to approximately two million of USA women. Various Authors have assumed a possible relationship between induction of ovulation and ovarian tumors. Between 1982 and 1997, at least 43 cases of ovarian tumors have been published (among these, there were also 25 cases of epithelial tumors) occurring in women previously treated with ovulation induction. The mean age of patient was 30.3 years, approximately 20 years younger than normal patient population for the same tumors. Among the possible causes of epithelial ovarian tumors, there is the trauma of the ovary surface caused by the continuous repeating of the ovulation phenomenon (incessant ovulation). Gynecologist should be aware of this potential risk for their patients. Multicentric studies should be evaluated in order to establish the risk of ovarian cancer in women treated for infertility problems. A survey of the international literature is made in order to analyse the epidemiological studies and to discuss the relationship between ovulation inducing agents and ovarian tumors.

Adult↗
PubMed1996

Physiologic basis of ovulation induction.

Optimal regimens for ovulation induction depend on a sound, fundamental understanding of the physiology of ovulation. This chapter will review the endocrinology of folliculogenesis, with particular emphasis on the signaling pathways activated by FSH and LH. Important new information regarding the molecular mechanisms of signal transduction and the biologic responses that are produced will also be presented. Ultimately, a clearer understanding of mechanisms regulating the selection and promotion of the dominant follicle, as described here, will lead to advances in the field of ovulation induction and pregnancy in women.

Female↗
PubMed2006

[Ovulation induction in anovulatory women].

Ovulation induction therapy is administered to stimulate follicular growth and induce ovulation in anovulatory infertile women. In anovulatory women with polycystic ovary syndrome, the treatment of choice is clomiphene citrate, whereas in clomiphene nonresponders, gonadotrophins are given as secondary therapy. Currently, insulin-sensitizing agents are used in the treatment of polycystic ovary syndrome to restore menstrual cyclicity. In selected patients, laparoscopic drilling has also been suggested. In anovulatory patients affected with hypogonadotropic hypogonadism, treatment is based on gonadotrophin replacement therapy or pulsatile gonadotrophin-releasing hormone infusion. In ovulation induction therapy the clinician's attention should be directed at restoring normal ovary function. When pharmacotherapy is required, monofollicular growth should be induced to reduce the risk of multiple pregnancy.

Anovulation↗
PubMed1986

Mild endometriosis and ovulatory dysfunction: effect of danazol treatment on success of ovulation induction.

The effectiveness of ovulation induction with clomiphene citrate or human menopausal gonadotropins was evaluated in 52 infertile women with stage I or stage II endometriosis and ovulatory dysfunction: anovulation or luteinized unruptured follicle (LUF) syndrome before (group I) and after (group II) danazol treatment. The incidence of anovulation and LUF in the endometriosis population was 9% and 34%, respectively. In group I, 10 of 36 patients (27.8%) conceived, with an average of 17.6 induction cycles per pregnancy. In group II, 21 of 30 patients (70%) conceived, with an average of 4.5 cycles per pregnancy (difference significant at P less than 0.001). There was no difference in the average number of ovulation induction cycles per patient between groups I and II (4.9 and 3.1, respectively). Of 14 patients who did not conceive in group I and crossed over to group II, 9 (64.3%) conceived (not different from group II). Spontaneous abortion rates were 20% in group I and 14% in group II. These results indicate that mild endometriosis may interfere with conception through mechanisms other than ovulatory dysfunction and that treatment with danazol appears to more than double the fertility rate.

Adult↗
PubMed2006

A new era in ovulation induction.

OBJECTIVE: To evaluate the efficacy of aromatase inhibitors in ovulation induction, superovulation, and IVF. DESIGN: A literature search was conducted with the key words "aromatase inhibitor," "letrozole," "anastrazole," "ovulation induction," "ovulation," and "superovulation" in MEDLINE, EMBASE, and the Cochrane Database of systematic reviews. RESULT(S): Ovulation induction with letrozole is associated with an ovulation rate of 70%-84% and a pregnancy rate of 20%-27% per cycle. In one study, ovulation and pregnancy rates with letrozole seemed to be higher than those of anastrazole. In superovulation, letrozole is associated with few developing follicles and thick endometrium. The use of letrozole for superovulation is associated with a pregnancy rate higher than with the use of clomiphene citrate (CC) (16.7% vs. 5.6%). The addition of letrozole to FSH treatment leads to a decreased FSH requirement. The pregnancy rate for treatment with letrozole and FSH was similar to that for FSH alone. CONCLUSION(S): Aromatase inhibitors are as effective as or superior to CC in ovulation induction and in superovulation. Unlike CC, they do not carry an antiestrogenic effect on the endometrium. Given the advantages of aromatase inhibitors, they can be used to replace CC as ovulation-inducing drugs. Their role in IVF remains to be determined.

Aromatase Inhibitors↗
PubMed2003

Prediction of chances for success or complications in gonadotrophin ovulation induction in normogonadotrophic anovulatory infertility.

This follow-up study evaluated whether initial screening characteristics predict treatment outcome of gonadotrophin induction of ovulation. One hundred and fifty-four women with normogonadotrophic anovulatory infertility for whom clomiphene citrate induction of ovulation was unsuccessful were included in the present study. Daily FSH injections were initiated on day 3-5 after spontaneous or progestagen-induced withdrawal bleeding. In most patients, a dose finding low-dose step-up regimen was applied during the first treatment cycle in order to identify the individual FSH response dose. In all subsequent cycles, a step-down protocol was applied. Initial serum concentrations of LH, testosterone and androstenedione were significant predictors for the probability of multi-follicular development. FSH treatment resulted in a total of 67 (44%) ongoing pregnancies. Comparing those women who did, versus those who did not, achieve an ongoing pregnancy in a multivariate Cox regression analysis, initial serum insulin-like growth factor-I (IGF-I), testosterone and women's age entered into the final model (AUC = 0.67). The individual treatment outcome following gonadotrophin induction of ovulation may be predicted by initial screening characteristics.

Adult↗
PubMed1992

[Ovulation induction with gonadotropins aided by cervix mucus analysis and echography].

Induction of ovulation was performed in 148 cycles using human menopausal gonadotropins (HMG) in 52 patients, seven with hypothalamic-pituitary failure and 45 suffering dysfunction at this level. Several induction schemes were used beginning on the second day of the cycle, until one or more follicles larger than 14 mm were found, to administrate 10,000 UI of human chorionic gonadotropin (HCG). Clinical valuation of cervical mucus and ultrasound of the ovaries to assess follicular development were done, from day eight of the cycle. Twenty five pregnancies resulted in 23 patients (44%), three in patients with failure and 22 in the dysfunction group. A total of 19 healthy babies were taken home, however three neonatal deaths, four miscarriages and one ectopic pregnancy occurred. Multiple gestation was present in three patients (12%), one was quadruplet, one triplet and one twin. The ovarian hyperstimulation syndrome (OHS) was detected in seven patients (13.4%), three were mild, two moderate and two severe; two cases of OHS had multiple pregnancies. Although induction of ovulation with HMG in patients with anovulation is a complex procedure requiring strict clinical vigilance and advanced technological resources, in this clinical study it was possible to obtain similar results to other series, using high resolution ultrasound only, without daily measurements of hormones.

Adult↗
PubMed1985

[Evolution of plasma levels of SHBG (sex-hormone binding globulin) during ovulation induction using gonadotrophins].

The plasma levels of proteins bound to steroids come under the influence of the levels of estrogens. This is why we have studied the changes in plasma SHBG in sterile women who were being treated by gonadotropins (HMG-HCG). The plasma level of SHBG was worked out using Laurell's electroimmunoassay technique with an autoradiographic display using estradiol labeled with I.125. It only takes 48 hours contact with radio films. Out of 12 patients 9 responded to the treatment as demonstrated by the plasma levels of estradiol (E2) and progesterone (P). We have found that in these women there was a rise in plasma SHBG which was significant from the 7th day of the treatment onwards (3.7 +/- 1.7 mg/l as against 5.9 +/- 2.6 mg/l, p less than 0.01) and this reached nearly twice the base level when E2 reached its maximum level (6.4 +/- 2.7 mg/l). When treatment was stopped the plasma level of SHBG dropped to that of the follicular phase, but it was out of step with the plasma E2 levels. The index of free E2 as compared with E2/TEBG showed a close superimposition when compared with the levels of E2 obtained using a radioimmunological method. This fact reinforces the value of plasma E2 as the way of monitoring the effect of induction of ovulation. Our overall conclusion is that a marked and rapid change in the level of plasma E2 directly influences the level of plasma SHBG. The consequences for treatment are that it is important to respect as far as possible the physiological conditions that are present when induction of ovulation is undertaken.

Estradiol↗
PubMed2004

Efficacy of metformin on ovulation induction in Asian women with polycystic ovary syndrome.

The aim of this study was to assess the efficacy of metformin on induction of ovulation in Asian women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Twenty PCOS women who did not respond to CC were enrolled in the study. All received 500-1500 mg/day of metformin for 4 weeks. If no dominant follicle was observed with monitoring by transvaginal ultrasound, 50-150 mg of CC per day for 5 days were added. Timing of sexual intercourse was determined or intrauterine insemination was carried out 36 h after administration of human chorionic gonadotropin. A total of six cycles, pregnancy or anovulation despite taking 150 mg of CC were considered as completion of the study. Blood samples were obtained before and at the end of the 4th week of treatment for hormonal assay. Ovulation was observed in 68 (89.5%) of 76 cycles, of which 34 (44.7%) occurred with metformin alone. Twelve women conceived; therefore, the pregnancy rate was 17.6% per ovulated cycle and 60% per woman. One (8.3%) had an abortion. Four women had minimal adverse effect, but one experienced a severe gastrointestinal effect during the fourth cycle. Insulin and androstenedione levels were significantly decreased after 4 weeks of treatment. In conclusion, these series demonstrated the excellent efficacy of metformin on induction of ovulation and pregnancy in Asian women with CC-resistant PCOS.

Adult↗