Outcome Of Ovulation Induction Research Articles

The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome.

In this study we examined the possible correlation between insulin metabolism and outcome of gonadotrophin stimulation in infertile clomiphene citrate resistant women with polycystic ovary syndrome (PCOS). The patient group comprised 42 women who were entered into the study in a consecutive fashion. Following performance of the CIGMA (continuous infusion of glucose with model assessment) test, 17 women were classified as insulin resistant and 25 women as non-insulin resistant. Each woman received up to two cycles of low-dose follicle stimulating hormone (FSH) stimulation starting with 75 IU of FSH for 1 week, giving a total of 70 cycles performed. The insulin resistant PCOS women required more gonadotrophin and a longer time to achieve follicular maturation. By multiple regression gonadotrophin consumption correlated best with CIGMA value but not with fasting insulin concentration or body mass index. In the insulin resistant PCOS women 10 out of 29 cycles were cancelled due to a multifollicular response, while only one of 41 cycles was cancelled in the non-insulin resistant PCOS women. Although ovulation rate in completed cycles was similar between the groups, the conception rate was significantly better in the non-insulin resistant PCOS women. In conclusion, in PCOS women insulin resistance seems to be an unfavourable condition resulting in an elevated cancellation rate and a low conception rate following low-dose FSH stimulation.

P-092. Ovarian morphometric analysis and ovulation induction outcome

P-092. Ovarian morphometric analysis and ovulation induction outcome

R-224. Canonical regression analysis in estimation of ovulation induction outcome in patients with PCOS

R-224. Canonical regression analysis in estimation of ovulation induction outcome in patients with PCOS

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

To avoid multiple pregnancies caused by ovulation induction. Infertile couples treated in the Women's Hospital and the Institute of Reproductive Medicine of the University of Münster, Münster, Germany. 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. Two hundred twenty-seven couples suffering from male infertility, unexplained infertility, incipient ovarian failure, and polycystic ovaries. Aspirations were performed if more than three follicles were sized > 14 mm. Number of (multiple) pregnancies. 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. 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.

Gonadotrophin-releasing hormone analogue as an adjunct to gonadotropin therapy for clomiphene-resistant polycystic ovarian syndrome.

Elevation of endogenous LH levels may result in premature luteinization. This may also be associated with the increased rate of spontaneous abortion. Gonadotropin releasing hormone analogue (GnRHa) used prior to human menopausal gonadotropin (hMG/FSH) administration may improve the outcome of ovulation induction. To assess if GnRHa pre-treatment plus FSH/hMG increase the rate of clinical pregnancy and/or decrease the rate of spontaneous abortion in women with WHO group 2 ovulatory dysfunction, compared with hMG/FSH alone. The Cochrane Subfertility Review Group specialised register of controlled trials was searched. All relevant published and unpublished RCTs were selected. Three RCTs were identified comparing these two approaches. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. Studies were clinically and statistically homogenous. Common odds ratios for pregnancy per treatment cycle and moderate to severe ovarian hyperstimulation syndrome (OHSS) were 1.50 (0.72-3.12) and 1.40 (0.5-3.92) respectively. These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.

Increased insulin secretion in patients with multifollicular and polycystic ovaries and its impact on ovulation induction

To assess the oral glucose tolerance test (OGTT)-stimulated insulin secretion and its relation to pulsatile GnRH ovulation induction outcome in patients with multifollicular or polycystic ovaries (PCOs). Prospective study. Reproductive Endocrinology Center, University of Bologna, Bologna, Italy. Eight normal and 29 anovulatory women (8 with multifollicular ovaries and 21 with PCOs). A standard OGTT was performed in all subjects. In all anovulatory patients, ovulation was induced with pulsatile GnRH (5 micrograms i.v. every 60 minutes). In multifollicular ovary patients, pulsatile GnRH was administered alone, whereas in PCOs it was preceded by GnRH agonist (GnRH-a) suppression. Glucose, insulin, and C-peptide response to the OGTT, expressed as area under the curve (AUC). Ovulatory rates in response to pulsatile GnRH. Insulin and C-peptide AUC were greater than controls in both multifollicular ovary and PCO patients. Insulin AUC was positively correlated to ovarian volume. Ovulation was achieved in 88% and 57% of multifollicular ovary and PCO patients, respectively. Body mass index and glucose AUC but not insulin and C-peptide AUC were significantly greater in the anovulatory PCO. [1] Insulin AUC was increased in both multifollicular ovary and PCO patients; [2] derangements of insulin secretion may be present in a greater variety of anovulatory patients than previously thought; [3] insulin levels during the OGTT did not predict a response to pulsatile GnRH in PCOs, suggesting complex insulin interactions at the ovarian level; [4] given the in vitro stimulatory properties of insulin on granulosa cells synergistic with FSH, we propose that excessive insulin levels may contribute to the ovarian enlargement often found in multifollicular ovary and PCO patients.

Immunoreactive inhibin levels during ovarian stimulation may predict granulosa cell maturity.

The aim of the study was to assess whether the immunoreactive inhibin response to ovarian stimulation in polycystic ovarian syndrome was of predictive value for the outcome of ovulation induction. Daily injections of purified FSH (Metrodin, Serono Laboratories, UK) were administered for the purpose of inducing development and ovulation of a single follicle. All patients had anovulatory infertility secondary to polycystic ovarian syndrome and were resistant to clomiphene citrate. Alternate day serum samples were obtained for measurement of gonadotrophins, sex steroids and inhibin by radioimmunoassay. Alternate day ovarian ultrasound scans were carried out to monitor follicular development. There was a high incidence of multiple follicular development (MFD) (10.2 +/- 7.1 (standard deviation) follicles). There was a close relationship between the number of follicles on the day of the ovulatory trigger and serum oestradiol (E2) levels (R = 0.97, P < 0.001). This relationship was not seen with serum immunoreactive inhibin levels (R = 0.31). The cycles were divided into two groups depending whether there was or was not MFD (more than five follicles > 7 mm in diameter on day of hCG administration). The MFD group had 15.6 +/- 8.5 follicles and the non-MFD group 3.2 +/- 1.6 follicles. There was no difference in the circulating E2 concentration (pmol/l) per follicle between the two groups (non-MFD cycles, n = 6,345 +/- 28.9; MFD cycles, n = 8, 308 +/- 40.29). However, the immunoreactive inhibin concentration (U/ml) per follicle was lower, P < 0.001, in the MFD group (4.3 +/- 1.6 vs 6.9 +/- 0.5). The maximum and mean follicle diameter were lower, P < 0.01, in the MFD group (maximum follicle size 16.5 +/- 3.9 vs 21.2 +/- 1.5 mm, mean follicle size 11.5 +/- 2 vs 14.9 +/- 2.3). When individual cycles were examined E2 and immunoreactive inhibin secretion rose in parallel in cycles with less than five follicles with a rapid rise occurring when the follicles reached about 12 mm in diameter. In cycles where there was MFD there was a disparity between E2 and immunoreactive inhibin secretion with E2 levels rising 4.3 +/- 1.4 days before immunoreactive inhibin levels. These data suggest that in cycles where there are multiple small follicles, E2 secretion is maintained whereas immunoreactive inhibin secretion is substantially lower. Thus, in view of the disparity between E2 and immunoreactive inhibin secretion evident in the MFD group, measurement of immunoreactive serum inhibin concentration may be a better indicator of granulosa cell maturity. Immunoreactive inhibin secretion may occur only from healthy mature follicles.

Effect of estrogen/progestin administration on the ovarian response to gonadotropins: a randomized, prospective study

The findings of our study indicate that women pretreated with E/progestin demonstrate increased gonadotropin requirements when undergoing ovulation induction. Whether this treatment has a significant effect on the outcome of ovulation induction in patients receiving gonadotropins remains to be established.