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Sonographic evaluation of the cervix during ovulation induction.

With the induction of ovulation, clomiphene citrate and human menopausal gonadotropin have the potential to stimulate the endocervical glands. We have found that the degree of mucus production can occasionally be quite large and hence is detectable by sonographic evaluation as an anechoic cervical mass. The incidence of this specific ultrasonic finding was found to be approximately 5%. This physiologic process should be differentiated from disease states affecting the cervix.

Adult↗

The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate.

OBJECTIVE: To assess the deleterious effect of clomiphene citrate (CC) on the development of the endometrium and its improvement by the addition of ethinyl estradiol (E2). PARTICIPATING PATIENTS: Infertility-treated patients, monitored for induction of ovulation or timing of insemination (control group). DESIGN: We studied four groups of women during an ovulatory cycle with various treatment schedules. Group 1: untreated patients; group 2: patients treated by CC; group 3: patients treated by CC + ethinyl E2; group 4: patients treated by human menopausal gonadotropin. Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2. RESULTS: In the group treated by CC, both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients. The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation. CONCLUSION: Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase.

Adult↗

Increased monozygotic twinning rate after ovulation induction.

Multiple births after artificial induction of ovulation (AIO) are usually considered to be due to fertilisation of multiple ova. In the East Flanders Prospective Twin Study between 1978 and 1985 the frequency of zygotic splitting after AIO (1.2%) was significantly higher than the expected frequency (0.45%) among spontaneous twins and triplets. Moreover, after AIO the frequency of zygotic division was significantly higher in triplets than in twins. AIO seems to be the first identified biological mechanism influencing the monozygotic twinning rate.

Female↗

[Follicular dynamics after treatment with hCG for ovulation induction in mares].

In this study the use of hCG for induction of ovulation is described. Factors such as follicle diameter at the time of administration of hCG (3000 IE hCG i.v.), follicular growth after hCG and the rate of double ovulations were evaluated. A total of 168 mares presented for artificial insemination were used. In 249 estrous periods hCG was given to mares exhibiting standing estrous when a minimum follicle diameter of 30 mm and a well developed edema of the endometrium could be detected by ultrasonography. In nine estrous periods ovulation occurred within 24 hours after hCG. The majority of mares (216; 86.7%) ovulated 24 to 48 hours after hCG and in 24 cases ovulation was delayed beyond 48 hours. Follicle size at the time of hCG administration (30-34 mm, 35-39 mm, > or = 40 mm) had no influence on the percentage of mares ovulating 24 to 48 hours after hCG (89.2%, 87.9%, and 83.7%, respectively). Double ovulations could be observed in 17.7% of estrous periods. The one cycle pregnancy rate was not influenced by follicle size (small 45.9%; medium 41.6%; large 47.5%). Repeated treatments with hCG during successive estrous cycles within one year did not influence the rate of responding to hCG. Mares in standing estrous respond well to hCG if a minimum follicle size of 30 mm and a well developed endometrial folding is present.

Animals↗

[Ovulation induction by the chronic administration of naltrexone in a patient with secondary hypothalamic amenorrhea].

An ovulatory cycle was induced by oral administration of a specific opiate antagonist: naltrexone, at a dose of 50 mg/day for 26 days in a woman suffering from secondary hypothalamic amenorrhea. The follicular growth was monitored by ultrasound and serial blood measurement of LH, FSH, E2 and progesterone. The hormonal and ultrasound profiles showed an ovulatory cycle with a single dominant follicle. After discontinuation of the treatment, the patient became amenorrheic again. The gonadotropin as well as estradiol plasma levels declined, to that observed before treatment. Naltrexone may be a useful agent for induction of ovulation in women suffering from hypothalamic amenorrhea.

Adolescent↗

Ovulation induction with a starting dose of 50 IU of recombinant follicle stimulating hormone in WHO group II anovulatory women: the IO-50 study, a prospective, observational, multicentre, open trial.

OBJECTIVE: To assess the efficacy and safety in clinical practice of a low dose regimen of 50 IU of recombinant follicle stimulating hormone in induction of ovulation. DESIGN: Prospective, observational, non-comparative, open, multicentre study. SETTING: Eighty-eight infertility clinics and teaching hospital fertility units throughout Spain. POPULATION: Women with normogonadotrophic chronic anovulation (WHO group II) with or without echographic diagnosis of polycystic ovary syndrome. METHODS: Low dose step-up protocol of recombinant follicle stimulating hormone administration (follitropin beta, Puregon) with a starting dose of 50 IU and weekly increments according to follicular response monitored prospectively by transvaginal ultrasonography. Patients were followed for a minimum of one cycle and a maximum of six. MAIN OUTCOME MEASURES: Rate and size of follicular growth, cumulative ovulation rate, follicle stimulating hormone doses and duration of treatment, pregnancy and cycle cancellation rate, ovarian hyperstimulation syndrome and multiple pregnancy. RESULTS: A total of 945 treatment cycles were evaluated. In 817 cycles, ovulation was induced with human chorionic gonadotrophin (hCG) and in 501 (61.3%) unifollicular development (a follicle of > or =18 mm) was achieved. A total of 128 cycles (13.5%) were cancelled because of ovarian hyper-responsiveness or spontaneous ovulation. The cumulative ovulation rate (confirmed by mid-luteal serum progesterone concentrations) after six treatment cycles was 84%. There were 136 clinical pregnancies (14.4% pregnancies per cycle). The cumulative pregnancy rate after six treatment cycles was 53.1%. Eight twin pregnancies occurred. Thirteen women miscarried and there were two cases of ectopic pregnancies. The median of average daily doses of follitropin beta in all cycles was 50 IU. Between 68% and 86% of patients received treatment with follitropin beta for a maximum of 14 days. Ovarian hyperstimulation syndrome occurred in 64 (6.8%) cases but no case of severe ovarian hyperstimulation developed. CONCLUSIONS: Low dose regimen of 50 IU of recombinant follicle stimulating hormone (Puregon) is efficient, safe and well tolerated for inducing follicular development in WHO group II anovulatory women.

Adult↗

[Indications for an increased risk of neural tube defects in pregnancies following ovulation induction and (or) in-vitro fertilization].

Several authors have reported a possible association between IVF or induction of ovulation on the one hand and the occurrence of neural tube defects on the other hand. Here a review is given of recent literature on this subject, including data available from The Netherlands. Collaborative epidemiologic studies are needed to evaluate the potential risks. In individual pregnancies prenatal examination is advised. In spontaneous abortions fetal pathological evaluation is desirable.

Abortion, Spontaneous↗

[Initial experiences in the use of pulsatile Gn-RH administration for ovulation induction].

In 9 patients the pulsatile administration of Gn-RH for the induction of ovulation was given in 13 treatments, we used the minipump Zyklomat of the firm Ferring and a Gn-RH pump from ZID Karlsburg. The administration was carried out for 10 to 18 days with dosages from 2.5 to 20 micrograms Gn-RH per pulse. 9 patients did ovulate and 5 patients became pregnant.

Adult↗

[Bromocryptin + gonadotropin vs. goserelin + gonadotropin in ovulation induction in patients with polycystic ovaries].

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with goserelin + HMG vs bromocriptine + FSH + HMG in the induction of ovulation in patients with ovarian polycystosis. EXPERIMENTAL DESIGN: A randomized prospective study. PATIENTS: Sterile women with ovarian polycystosis of the first type not responding to clomiphene citrate. TREATMENT: Group A: bomocriptine + FSH + HMG (10 patients); Group B: goserelin depot (Zoladex) + HMG (18 patients). RESULTS: A greater percentage of ovulations, pregnancies and a higher success rate were obtained in Group B. The percentage of hyperstimulation was similar in both groups; there was a higher percentage of abortion in Group A. Cycle duration and the number of phials of gonadotropin were greater in Group B. CONCLUSIONS: Treatment with bromocriptine + gonadotropin remains the simplest; the treatment protocol based on geserelin depot + gonadotropin proved to be more efficacious.

Adult↗

[The use of growth hormone (hGH) in ovulation induction in women].

Number of in vitro experiments have shown increasing evidence for local ovarian actions of GH by demonstrating: the presence of receptors for GH in human granulosa cells; the ability of GH to enhance estradiol (E2) production by human granulosa cells withdrawn in late follicular phase; the increasing effect of GH on progesterone (P) biosynthesis by human luteal cells. Moreover, GH being the main regulator of IGF-I plasma levels, its indirect effect by means of hepatic and/or ovarian IGF-I production remains possible. Few patients have been included in randomized studies using hGH with gonadotropins for induction of ovulation and their selection criteria were heterogeneous so that no definitive conclusion can be drawn about the beneficial effect of GH in facilitating ovulation. The reduction both in duration of stimulation and in the requirement for menopausal gonadotropins found in some studies have been challenged by others. The recombinant human growth hormone (hGH) is able to modify the game of intraovarian regulators and may affects ovocyte and embryo. Such a potential impact cannot be occulted, justifying to develop larger in vivo animal experimentation before new further clinical studies.

Clinical Trials as Topic↗

Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments.

The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process.

Adult↗

Ovulation induction.

Induction of ovulation is indicated for anovulatory and amenorrheic women as well as for women who have an inadequate luteal phase. It is also indicated as a strategy for recruiting multiple follicles for women with unexplained infertility and those who are undergoing assisted reproductive technologies. The use of various agents and detection of ovulation are described. This includes a discussion of clomiphene citrate, bromocriptine, human menopausal gonadotropins, urinary follicle stimulating hormone and pulsatile gonadotropin releasing hormone therapy. Regimens, success rates and potential complications of each form of therapy are reviewed. Also discussed is the use of combination therapy and partial ovarian destruction.

Bromocriptine↗

[Evaluation of ovulation induction in infertile women who are underweight].

The induction of ovulation in 74 underweight normally menstruated sterile women were analyzed with regard to the body mass index (BMI). The underweight patients presented 10.5% of the treated anovulatory women among them 4.8% presented serious weight loss. The concentration of serum gonadotropins and estradiol just before treatment did not allow to anticipate the results of therapy. The interesting observation concerned the cases with low concentration of serum FSH and LH which was more frequently found in nonresponding patients. The ovulatory ratio was not high and was comparable in all groups but pregnancy ratio in the responders was 1.5 times higher in slightly underweight patients. Among the nonresponders more than half of them demonstrated follicular growth confirmed by USC, serum estradiol and mucus viscosity.

Adult↗

Use of growth hormone-releasing factor in ovulation induction in poor responders.

OBJECTIVE: To evaluate the effect of growth hormone-releasing factor (GRF), given in addition to follicle-stimulating hormone (FSH), after pituitary down-regulation, on follicular development in poor responders. GRF was added in a prospective, randomized manner to an existing stimulation protocol. STUDY DESIGN: Forty-two women, demonstrated to be poor responders in previous attempts at induction of ovulation, were included in the study. Follicular stimulation with FSH was started after pituitary downregulation obtained using gonadotropin-releasing hormone agonist (GnRH-a). GRF, 1,000 mg/day, was given in addition to FSH to 22 patients randomly chosen until human chorionic gonadotropin administration. RESULTS: The number of ampules of FSH needed to obtain follicular growth was significantly reduced in the group of women who received GRF. Also, the number of follicles obtained was higher and the days of treatment generally reduced. However, a greatly beneficial effect for some women was observed, while a second subgroup did not have any. No differences were observed in follicular steroid and insulin growth factor 1 (IGF-1) between GRF patients and controls or in serum IGF-1 between the two subgroups of patients who received GRF. CONCLUSION: In vivo administration of GRF with FSH after pituitary down-regulation may be beneficial for some poor responders, although prognostic criteria could not be established. However, the use of GRF does not seem to influence the chance of obtaining pregnancy; it remains low in these patients.

Adult↗

[A murine model of polycystic ovaries: its use in the evaluation of effects of endoscopic ovulation induction].

The objective was to evaluate the effect of the endoscopic treatment of the polycystic ovary syndrome (PCOS) in a murine model induced with depot estrogen. Three groups with PCOS were studied: group 1 (n = 22) evaluated exclusively using laparoscopy; group 2 (n = 11) one fulguration on both ovaries was performed during laparoscopy; and group 3 (n = 10) three fulgurations were performed. One month after laparoscopy the animal were sacrificed and was carried surgical microscopic examination of the intraabdominal organs, moreover histological evaluation of the gonads was practiced. All the animals showed PCOS. No adhesions were observed in the animals of group 1, while the frequency of adhesion in group 2 was 36.3%, 18.1% of the animals of group 2 showed gonadal atrophy. The frequency of adhesions in the group 3 was 66.6%. The adhesion score was significantly higher in groups 2 and 3 than in group 1. Is concluded that the use of estrogen is useful to induce PCOS in animal models. The procedure can be employed to study the effects of the surgical induction of ovulation, it's utility in other conditions seems promissary.

Animals↗

Polycystic ovary syndrome and ovulation induction.

Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory infertility. Although many options are available for ovulation induction in these patients, there is currently no evidence-based algorithm to guide the initial and subsequent choices of ovulation induction methods. In obese women with PCOS, mild to moderate weight loss results in improvement of ovulatory dysfunction, and should be advocated at the onset of the evaluation. Clomiphene citrate is currently the 1st line medical therapy for ovulation induction. Glucocorticoids do not result in consistent ovulation and have significant side effects. Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a high risk of miscarriage. The most commonly used medical agents for ovulation induction in clomiphene-resistant women with PCOS are parenteral gonadotropins. Various gonadotropin preparations and different protocols are available; however the risk of multiple pregnancy and ovarian hyperstimulation is high with gonadotropin therapy. The frequent association between PCOS and insulin resistance has prompted recent studies on the effect of insulin-sensitizing agents on spontaneous and as an adjuvant to conventional ovulation induction therapies. Overall, the improvement in ovulation with insulin sensitizing drugs is modest, and unresolved issues such as variability in ovarian response remain to be addressed in future studies. Nevertheless, these agents may be beneficial in a subset of PCOS patients. Surgical ovulation induction methods such as ovarian diathermy have been reported to be moderately effective. However, due to the inherent associated risks and unknown effect on long-term reproductive potential, this modality should be reserved for patients who are clomiphene-resistant and unable or unwilling to proceed to gonadotropin therapy.

Female↗

Experience with transvaginal ultrasound-guided aspiration of supernumerary follicles for the prevention of multiple pregnancies after ovulation induction and intrauterine insemination.

OBJECTIVE: To avoid multiple pregnancies caused by ovulation induction. SETTING: Infertile couples treated in the Women's Hospital and the Institute of Reproductive Medicine of the University of Münster, Münster, Germany. DESIGN: The outcome of ovulation induction in patients in whom supernumerary ovarian follicles were aspirated transvaginally was compared with the outcome in patients in whom this intervention was not necessary. In a second randomized prospective study, the efficacy of a low dosage of gonadotropins was compared with a higher dosage. PATIENTS: Two hundred twenty-seven couples suffering from male infertility, unexplained infertility, incipient ovarian failure, and polycystic ovaries. INTERVENTIONS: Aspirations were performed if more than three follicles were sized > 14 mm. MAIN OUTCOME MEASURE: Number of (multiple) pregnancies. RESULTS: During 232 ovulation inductions, 127 aspirations of supernumerary follicles were performed (54.7%). The pregnancy rate (PR) in these cycles was similar to cycles in which aspirations were unnecessary (24.4% versus 21.9%). The efficacy of 75 units of FSH administered daily during the recruitment phase of follicular development was equivalent to 150 units of FSH (PR: 32.4% versus 31.6%), but supernumerary follicles were fewer (26.5% versus 76.3%). Six twins, two triplets (multiple PR: 10.4%), and no ovarian hyperstimulation syndrome occurred. CONCLUSIONS: Transvaginal aspiration of supernumerary follicles does not reduce the PR in ovulation induction. Supernumerary follicles can be avoided by low-dose administration of gonadotropins without compromising the PR.

Female↗