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PubMed1980

[Maturation and in vitro fertilisation of human oocytes recovered after spontaneous ovulation or after induction of ovulation by use of gonadotrophins (preliminary results) (author's transl)].

Maturation and/or in vitro fertilisation of human oocytes was carried out on 70 oocytes recovered from 56 young women who had normal periods and were having laparoscopy for tubal sterility. Five oocytes were recovered in the pre-ovulatory phase of spontaneous cycles by the use of ultrasound determination of follicular growth and the presence of an LH peak estimated from urine levels. 65 oocytes were obtained by puncture of follicules that had been stimulated using HMG/HCG 32-36 hours after HCG had been injected. 66 per cent of these eggs showed signs of degeneration before culture. The immature oocytes which were cultured for 42-46 hours at 36 degrees C with or without gonadotrophins underwent meoisis in 80 per cent of cases and 41 per cent expelled their first polar body. None of these oocytes could be fertilised in vitro, whereas 50 per cent of the oocytes that were recovered in metaphase II and fertilised in vitro had reached the stage of pronuclei 20 hours later. Ultrastructural and cytogenic studies will be carried out to ascertain the quality of these eggs before any attempt is made to reimplant.

Adult↗
PubMed1999

Polycystic ovary syndrome. Insulin resistance and ovulatory responses to clomiphene citrate.

OBJECTIVE: To evaluate insulin secretion detected on oral glucose tolerance testing in relation to clomiphene citrate (CC) responses in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: A total of 37 PCOS women were enrolled. Plasma baseline levels of gonadotropins, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulfate and testosterone (T) were determined. Insulin and glucose serum concentrations were analyzed in all samples after a 75-g oral glucose tolerance test. A dose of 100 mg/d of CC was given for ovulation induction. Ovulation was detected by ultrasonographic observation in conjunction with a serum progesterone level. RESULTS: During three consecutive cycles of CC administration, two or more anovulatory cycles were observed in 12 of 37 PCOS women (defined as CC nonresponders). The serum T level and the area under the curve (AUC) of insulin were significantly higher in CC nonresponders. The receiver operating characteristic curve of the AUC of insulin provided the most appropriate cutoff point for the prediction of CC resistance. CONCLUSION: We found higher androgen secretion and insulin resistance in CC nonresponders. The AUC of insulin was the most reliable method for the prediction of CC resistance associated with insulin resistance.

Adult↗
PubMedDate not supplied

[Pulsatile treatment with gonadotropin-releasing hormone (GnRH)].

The different ways of administration condition the frequency of the pulsatile GnRH, because of the different rate of depot. High frequencies (60-90/min) can be reached only with the intravenous route which is suitable for ovulation induction: ovulation is reached in 73-92% of women affected by hypothalamic amenorrhoea and in 41-51% of women affected by polycystic ovarian syndrome (previously suppressed with buserelin); overstimulation risk is lesser than during therapy with gonadotropins. Subcutaneous route is suitable for puberty induction which needs long-term treatment (18-24 months); the results are generally good, except in hypopituitaric patients. Intranasally route needs frequencies greater than 150-180 min: low frequencies administration (3 times/day) is sufficient to treat cryptorchidism and to reach good results (30-70%); moreover intranasally route can be useful to maintain the results reached with long term therapy with LHRH or gonadotropins.

Gonadotropin-Releasing Hormone↗
PubMed1989

IVF: induction of ovulation in poor responders.

All IVF programs have a consistent rate of failure in inducing ovulations. Pharmacological induction of ovulation is otherwise crucial for an IVF program because of the need for more than one ovum. Since it is well known that the best candidates for HMG treatment are hypogonadotropic women a short reversible hypogonadotropic state was induced in IVF patients by LH-RH agonist (Buserelin). Superovulation was then achieved with very high initial doses of FSH (Metrodin) in order to maximize the ovarian response. This technique used in 116 IVF women induced a satisfactory follicle growth even in 70% of the patients already poorly responsive to HMG stimulation.

Adult↗
PubMed2004

Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.

OBJECTIVE: To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. DESIGN: Randomised controlled trial. SETTING: Secondary and tertiary hospitals in the Netherlands. PARTICIPANTS: 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. INTERVENTION: Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. MAIN OUTCOME MEASURE: Ongoing pregnancy within 12 months. RESULTS: . The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). CONCLUSION: The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy.

Adult↗
PubMed2001

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate.

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.

Anovulation↗
PubMed1988

Induction of ovulation in the patient with polycystic ovarian disease.

Induction of ovulation is difficult to achieve in patients with PCOD when they are resistant to therapy with clomiphene citrate; moreover, treatment with human menopausal gonadotropins subjects the PCOD patient to the risk of multifollicular ovulation and hyperstimulation. This article summarizes the hormonal picture and the initial therapeutic approach to the patient with PCOD. The proper administration, usage, and monitoring of conventional ovulation-inducing agents for these patients are discussed. Some of the newer approved agents that can be used in special patients who have not responded to conventional ovulation induction are also described.

Androgens↗
PubMed1983

Induction of ovulation by prolonged pulsatile administration of luteinizing hormone releasing hormone (LRH) in patients with clomiphene resistant polycystic ovary-like disease.

Induction of ovulation with pulsatile administration of LRH by automatic portable infusion pump for 74 and 147 consecutive days in 2 patients with clomiphene resistant PCO-like disease is described. The patients exhibited 6 ovulatory cycles. One patient conceived during the fourth cycle. During the treatment a unilocular cyst, probably a lutein cyst, developed in one patient, but subsequently disappeared spontaneously under uninterrupted therapy. No chemical hyperstimulation was observed. Follicular phases lasted for 32 and 13 days in patient I and for 19, 25, 14 and 22 days in patient II. Luteal phases lasted for 16 and 15 days in patient I and for 17, 18 and 15 days, respectively in patient II. Total urinary oestrogen and pregnanediol excretion did not differ from that seen in normal cycles. LH baseline and peak values and LH responses declined to normal levels accompanied by a normalization of the LH/FSH ratio during pulsatile LRH treatment in both patients. The first pre-ovulatory episode occurred already after partial normalization of the LH/FSH ratio. The endocrinology of the second LRH induced cycles of patients I and II was not different from cycles similarly induced in hypogonadotrophic patients. We conclude that ovulation induction with pulsatile LRH administration in patients with clomiphene resistant PCO-like disease is possible. Our findings give hope that this mode of treatment may not only be effective, but may prove to be safer than ovulation induction with menopausal gonadotrophins in patients with clomiphene resistant PCO-like disease.

Adult↗
PubMed1981

Monitoring induction of ovulation by rapid radioimmunoassays of oestrogen and pregnanediol glucuronides.

To increase the sample-handling capacity for an induction of ovulation programme, direct urinary radioimmunoassays (RIA) for three steroid glucuronides, pregnanediol-3-glucuronide (Pd-3-G), oestrone-3-glucuronide (E1-3-G), and oestriol-16 alpha-glucuronide (E3-16-G), were established. Results obtained for urinary Pd-3-G measured by direct RIA show an excellent correlation (r = 0.98, N = 46) with those for urinary pregnanediol measured by gas-liquid chromatography. Estrone-3-glucuronide (E1-3-G) and estriol-16 alpha-glucuronide (E3-16-G) values, measured by direct RIA, closely paralleled the total urinary oestrogen measured fluorimetrically. Ovarian response to ovulation induction therapy can be monitored by observing the changes in the levels of E1-3-G in urine. Pre-ovulatory levels of urinary E3-16-G were found to be too low for use in this regard. Direct RIA for E1-3-G and Pd-3-G are recommended as reliable indices of ovarian function in the monitoring of patients receiving treatment for the induction of ovulation.

Animals↗
PubMed1996

Hypogonadotropic patients with ultrasonographically detected polycystic ovaries: endocrine response to pulsatile gonadotropin-releasing hormone.

To characterize the endocrine response during induction of ovulation in patients with hypogonadotropic hypogonadism and ultrasound findings of polycystic ovary, we performed a retrospective analysis of 22 treatment cycles with pulsatile gonadotropin-releasing hormone (GnRH) in such patients and of 17 treatment cycles in similar patients with ultrasonographically normal ovaries. Of the 21 patients studies, 11 had an ultrasound finding of polycystic ovaries and ten had ovaries that appeared normal. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol levels, number of follicles of diameter > 12 mm (by ultrasound), and ovulation and conception rates were measured. Patients with hypogonadotropic hypogonadism and ultrasound-diagnosed polycystic ovary had pretreatment endocrine status similar to those with normal ovaries, but had much higher baseline ovarian volume. Ovulation induction with pulsatile GnRH induced much higher serum LH concentrations in the former group despite similar FSH levels. This difference preceded any change in estradiol levels. The former group consistently recruited significantly more follicles during pulsatile GnRH treatment. However, ovulation and conception rates were (non-significantly) higher in the latter group. In conclusion, this study characterized a subgroup of hypogonadotropic patients with ovarian morphology, volume and response to ovulation induction similar to in patients with polycystic ovary syndrome. When treated with pulsatile GnRH, those with polycystic ovary significantly hypersecreted LH before their estradiol level changed significantly. The primary lesion in polycystic ovary syndrome seems to be in the ovary, with pituitary hypersecretion of LH secondary to disturbed ovarian feedback signalling.

Estradiol↗
PubMed1999

[Treatment of polycystic ovary syndrome and related infertility with clomiphene resistance by compound cyproterone acetate].

OBJECTIVE: To assess the efficacy and safety of compound cyproterone acetate (CPA Co, or Diane-35) in the treatment of polycystic ovary syndrome (PCOS) and to explore its potential role in improving the outcome of ovulation induction in clomiphene (CC) resistant cases. METHODS: Twenty-nine proven PCOS patients were enrolled. Seventeen out of them, including 16 who were resistant to CC, had anovulatory infertility. CPA Co was given for 4-6 cycles. Serum luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), testosterone(T), androstenedione(A), dehydroepiandrosterone (Ds), sex hormone binding globvlin (SHBG), insulin concentrations, total cholesterol, triglycerides(TG), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A, apolipoprotein B and transvaginal pelvic ultrasonography were determined before, 2-3 cycles and 4-6 cycles after treatment. After stopping the drug, CC or human menopausal gonadotropin were re-administered in 12 patients (22 cycles) and 5 cases (6 cycles) respectively for induction of ovulation. RESULTS: All patients had regular uterine bleeding during CPA Co therapy. Acne improved in 8 cases. Hirsute score didn't decrease significantly. Serum LH, FSH, E2, A, T, Ds concentrations decreased significantly (P < 0.05-0.01), while SHBG levels increased by 5.1 times after treatment. Meanwhile, bilateral ovarian volumes shrunk and follicle numbers decreased significantly (P < 0.05-0.01). Serum insulin levels did not change significantly. As to the lipid profile, the most striking change was 55.1% increase of HDL-C and 23.0% decrease of LDL-C, although TG also increased by 36.2%. 58.6% of patients had mild and transient adverse effects. Serum alanine transaminase increased in 3 cases. After stopping treatment, CC induced 5.3% (by cases) or 45.4% (by cycles) ovulation rate and 2 pregnancies achieved in 12 CC resistant patients. CONCLUSION: CPA Co has antiandrogenic effects on PCOS patients clinically, biochemically and in ovarian morphology. Pretreatment of CPA Co may play a role in improving the outcome of ovulation induction in CC resistant cases.

Adult↗
PubMedDate not supplied

In vitro fertilization and embryo transfer: a brief overview.

The in vitro fertilization process breaks down into three essential components: induction of ovulation, fertilization of the oocyte, and development of embryos that are transferred into the uterus. Problems may arise resulting in failure at any one of these junctions. In 1984, the World Congress on In Vitro Fertilization was held, looking at 9,641 laparoscopies yielding 1,101 clinical pregnancies, with an overall pregnancy rate of 11 percent--clearly indicating that in vitro fertilization/embryo transfer (IVF/ET) was an idea whose time had come. Ovulation induction is monitored by both the use of ultrasound and daily estradiol levels, ultrasound indicating the number of oocytes that will be available for capture, and estradiol indicating in an indirect way the quality of those oocytes. It is a major aim in each patient to obtain at least four embryos, since this optimizes success rates. Ovulation induction at Yale is carried out with a high-dose human menopausal gonadotropin (HMG)/human chorionic gonadotropin (HCG) regimen. This regimen has insured us a success rate of 17 percent clinical pregnancies per laparoscopy. In the future, modification will occur in the process with cryopreservation of oocytes and embryos, and gamete manipulation. The modifications will be effected primarily to increase pregnancy rates. Research will continue mainly to delineate better biochemical markers for oocyte quality, but also to further explain the mystery of implantation.

Embryo Transfer↗
PubMedDate not supplied

Severe ovarian hyperstimulation syndrome. Case reports.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovulation induction. It is most often associated with the administration of human menopausal gonadotropins (hMG) or purified preparation of follicle stimulating hormone (FSH), but has also been reported after clomiphene (CC) and in patients with hydatiform mole and chorioepithelioma. Moreover, OHSS has been observed in cases of multiple pregnancy unrelated to the use of fertility drugs. In recent years, the hormonal induction of ovulation has been practised to an increasing degree, partly due to the extended use in vitro fertilization (IVF) and gamete intra fallopian transfer (GIFT) techniques in the treatment of infertility. This trend will undoubtedly result in a growing number of patients with OHSS: For this reason, it is important to elucidate the pathophysiological mechanisms responsible for trigging this condition and discuss the treatment possibilities once it has arisen. We will present three patients who developed OHSS after different attempts at ovulation induction. Interestingly, aspiration of the follicles, which was carried out in two of the cases, did not influence the progress of the condition.

Adult↗
PubMed2006

Validation of a prediction model for the follicle-stimulating hormone response dose in women with polycystic ovary syndrome.

OBJECTIVE: To validate a published model for the prediction of the individual FSH response dose for gonadotropin induction of ovulation in polycystic ovary syndrome (PCOS). DESIGN: Structured, complete, and carefully monitored patient-based data collection to test the external validity of the prediction model. SETTING: Twenty-nine hospitals in The Netherlands. PATIENT(S): Eighty-five clomiphene citrate (CC)-resistant women with PCOS. INTERVENTION(S): Ovulation induction in a chronic low-dose step-up FSH regimen. MAIN OUTCOME MEASURE(S): Predicted individual FSH response dose, defined as follicle growth >10 mm in diameter on ultrasound. RESULT(S): The model, using the women's body mass index, CC response, initial serum FSH level, and initial serum insulin-to-glucose ratio was studied in the validation sample. Overall, the FSH response dose predicted by the model was higher than the observed response dose. The predictive performance of the model was poor, with an R(2) of 0.11, and the average prediction error was 35 IU. CONCLUSION(S): The external validity of the model predicting the individual FSH response dose was inadequate in women with CC-resistant PCOS undergoing ovulation induction with recombinant FSH in a low-dose step-up regimen.

Adult↗