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PubMedDate not supplied

IVF outcome in anovulatory infertility (WHO group 2)--including polycystic ovary syndrome--following previous unsuccessful ovulation induction.

This follow-up study represents IVF treatment characteristics and outcomes in women with World Health Organization (WHO) group 2 anovulatory infertility after previous unsuccessful ovulation induction compared with controls. Furthermore, the possibility of initial screening parameters of these anovulatory women to predict IVF outcome was examined. Twenty-six patients with WHO 2 anovulatory infertility who failed to achieve a live birth following previous induction of ovulation (using clomiphene citrate as first line and exogenous FSH as second line) were compared with 26 IVF patients with tubal infertility matched for age, treatment period and treatment regimen. The WHO 2 patients underwent 49 IVF cycles, whereas the normo-ovulatory controls underwent 46 cycles. In WHO 2 patients 15 cycles were cancelled compared with six cycles in controls (P = 0.04). Cycles were predominantly cancelled due to insufficient response (P = 0.04). In cases in whom the cycle was cancelled, body mass index (BMI) was significantly higher (P < 0.001) in WHO 2 women compared with controls. Overall live birth rates were comparable (P = 0.9). Obese women suffering from WHO 2 anovulatory infertility are at an increased risk of having their IVF cycle cancelled due to insufficient response. Once oocyte retrieval is achieved, live birth rates are comparable with controls.

Adult↗
PubMed1994

Ovulation induction and endometrial steroid receptors.

The endometrial morphology, endometrial steroid receptors and serum steroid hormone concentrations have been studied in 22 infertile women participating in an in-vitro fertilization, gamete intra-Fallopian transfer programme, including nine cases following treatment with gonadotrophin-releasing hormone analogue/human menopausal gonadotrophin/human chorionic gonadotrophin. All patients had normal ovulatory function before treatment and satisfactory response to ovulation induction. Endometrial biopsies were taken in spontaneous and treatment cycles on the fourth day after ovulation had been detected by ultrasound scanning, when endometrial receptors were measured using immunohistochemistry. Histological examination of biopsies in spontaneous cycles showed the majority (20/22) to be 'in-phase', while in two cases luteal phase defect was diagnosed. After ovulation induction, all the biopsies were still morphologically 'in-phase', although a significant reduction had occurred in the nuclear receptor level in both the glands and stroma for both progesterone receptors (gland P = 0.030, stroma P = 0.012 using microscopic analysis; gland P = 0.020, stroma P < 0.001 using a cell analysis system) and oestrogen receptors (gland P = 0.017, stroma P = 0.002 using direct microscopic analysis). This suggests that a reduction in steroid receptors in the endometrium occurs after ovulation induction in the presence of supraphysiological amounts of steroids, which is not associated with detectable morphological changes.

Adult↗
PubMed1994

Sonographic uterine predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments.

OBJECTIVE: To determine preovulatory uterine sonographic predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments. DESIGN: Prospective evaluation of uterine sonographic and vascular flow profiles in women stimulated with leuprolide acetate and hMG. SETTING: Private fertility center and tertiary-care academic center. PATIENTS: Ninety-six women underwent 102 cycles of ovulation induction for IVF (46), GIFT (20), and zygote intrafallopian transfer (36). MAIN OUTCOME MEASURES: Endometrial texture, thickness, resistance index at the first branch of uterine artery, diastolic blood flow, and pregnancy outcome (no conception, spontaneous abortion, and delivery). RESULTS: Triple-lined pattern was predominant in women who delivered liveborn infants (P < 0.005). Endometrial pattern and diastolic blood flow were the only predictive markers of term pregnancy (P < 0.001 and P < 0.05, respectively). CONCLUSION: Preovulatory triple-lined sonographic endometrial texture and the presence of end diastole blood velocities at the first branch of uterine artery are the most important uterine predictors of conception.

Adult↗
PubMed1994

Low-dose follicle stimulating hormone for ovulation induction in polycystic ovary syndrome.

In 20 patients with clinically, sonographically and endocrinologically proven polycystic ovary syndrome, ovulation induction with low doses of follicle stimulating hormone (FSH) was attempted by administration for 27 menstrual cycles. One ampule FSH was administered from day 3 onwards. If the ovarian response was inadequate after days 10-12, the daily FSH dose was increased by half an ampule until ovulation induction. Of the cycles, 55.5% were monofollicular, whereas 4 cycles had to be cancelled due to a multifollicular response or failure of ovarian stimulation. On average, 14.4 ampules was used, and human chorionic gonadotropin was given on day 16. Seven pregnancies were established, with all of them ongoing at this writing. One twin pregnancy and one triplet pregnancy occurred. Even in polycystic ovary syndrome patients, low-dose administration of FSH allows safe stimulation, with a low incidence of ovarian hyperstimulation, a high pregnancy rate and an acceptably low risk of multiple pregnancies.

Adult↗
PubMed1987

Ovulation induction.

Methods to induce ovulation in anovulatory women have blossomed over the last three decades. The introduction of clomiphene citrate in 1960 allowed us for the first time to provoke follicle development in patients with normo or hyperestrogenic forms of anovulation. The development of human menopausal gonadotropins in the early 1960s gave us a much more powerful tool with which to influence ovulation in all forms of ovulatory disturbances. Elucidation of the pulsatile secretion of gonadotropin-releasing hormone together with its isolation and synthesis has allowed us to streamline our methods of inducing ovulation in hypothalamic amenorrheic patients by using endogenous control mechanisms to maximize both safety and effectiveness. However, there are problems yet to solve. Polycystic ovarian disease has long eluded our efforts to resolve its pathophysiology as well as to devise a consistently effective and safe means of treatment. Methods to restore ovulation in patients with polycystic ovarian disease refractory to clomiphene citrate is the quest of future investigations.

Animals↗
PubMedDate not supplied

Use of new biologic markers in the ovulation induction.

Biological markers of ovulation, after a great in the past, have been fallen into disuse for the large diffusion of biochemical and biophysical ones. However, the real effect of hormones involved in ovulation is expressed by biological modifications on target tissues. To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia, Platelet Factor IV (as indicator of Platelet Aggregation), Type II estrogenic receptors in 42 ovulation induced women, undergoing our observation. 33 of them had ovulation and 9 developed a LUF syndrome, constituting two biological models of an opposite situation for the three markers observed. All the markers considered were sufficiently sensitive, but among them, Platelet Factor IV was the most reliable to the hormonal ovulatory situation.

Biomarkers↗
PubMed1995

Evolution of clinical agents for ovulation induction.

Since the first use of human urinary gonadotropins in the 1960s, the number of agents available for ovulation induction has remained fairly static. However, the nature of gonadotropin therapy is expected to change rapidly in the near future, and by the end of the decade these changes may be augmented by nongonadotropin ovulation induction therapies. Newer agents described in the literature include highly purified preparations of follicle-stimulating hormone and recombinant forms of follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Protein fragments, cytokines, and growth factors also show great promise as ovulation adjuncts. Other promising approaches being explored are the use of genetically engineered human gonadotropin derivatives, the creation of chimeric proteins, and gene therapy.

Animals↗
PubMed2003

Follicular response and pregnancy among infertile women undergoing ovulation induction and intrauterine insemination.

OBJECTIVE: To determine the relationship between ovarian follicular response (number and diameter of follicles) to ovulation induction agents and pregnancy. DESIGN: Retrospective cohort study.Hospital-based center of reproductive medicine. PATIENT(S): Three hundred twenty-two clinically diagnosed infertile couples undergoing 1483 cycles of ovulation induction and IUI. Oral and injectable fertility drugs were administered for 2-10 cycles; ultrasound follicular measurements were recorded around time of ovulation; hCG was administered when follicles were 18-20 mm or more in diameter; IUI was performed 36-40 hours after administration of hCG. MAIN OUTCOME MEASURE(S): A first positive pregnancy test as indicative for conception. Women with follicular diameters >or=20 mm were less likely to become pregnant as compared to women with diameters between 15.00 and 19.99 mm (risk ratio [RR] = 0.58, 95% confidence interval [CI] = 0.35, 0.97). Women >or=30 years of age were half as likely to become pregnant as compared to women <30 years (RR = 0.51, 95% CI = 0.30, 0.85). Likelihood of pregnancy increased by 21% for each prior pregnancy (RR = 1.21, 95% CI = 1.00, 1.47). CONCLUSION(S): Maternal age, gravidity, and follicular diameters around the time of insemination are prognostic factors in the likelihood of pregnancy.

Cohort Studies↗
PubMed1997

Influence of ovulation induction with human menopausal gonadotropin on uterine blood flow: comparison of unexplained and mechanical infertility.

A prospective study in patients undergoing in vitro fertilization treatment was conducted to assess whether any difference may be present in uterine blood flow between unexplained and mechanical infertility, before and during ovulation induction. The ascending branch of the uterine artery, the arcuate arteries, and the radial arteries were examined by transvaginal, color pulsed Doppler sonography on day 3 and on the day of human chorionic gonadotropin administration. Patients with mechanical factor demonstrated a decrease in resistance to blood flow in all the examined vessels during ovulation induction. Patients with unexplained infertility showed a contrasting trend in changes of uterine blood flow (e.g., as the cycle progressed, the resistance index increased). Moreover, the resistive index values on the day of human chorionic gonadotropin administration were significantly higher in patients with unexplained infertility. It is quite possible that the rise in impedance to uterine blood flow during ovulation induction and the higher impedance on the day of human chorionic gonadotropin administration in patients with unexplained infertility may be one of the factors responsible for the lower conception rate in these patients.

Arteries↗
PubMed2003

Ovulation induction--optimizing results and minimizing risks.

The aim of ovulation induction therapy should be, wherever possible, to correct the underlying disturbance and achieve safe, repeated unifollicular ovulation to achieve the live birth of singleton babies. This article outlines the main causes of anovulatory infertility but deals mostly with the management of anovulatory polycystic ovary syndrome (PCOS), which is the most common problem to confront specialists in reproductive medicine. PCOS is associated with insulin resistance, particularly in those who are overweight. Thus, strategies to achieve weight loss and improve insulin sensitivity, including the use of drugs such as metformin, enhance reproductive function. Therapies to induce ovulation involve first the use of the anti-oestrogen clomiphene citrate. For those who fail to ovulate in response to clomiphene citrate, the principal options include parenteral gonadotrophin therapy or laparoscopic ovarian diathermy.

Adult↗
PubMed2001

Successful ovulation induction, conception, and normal delivery after chronic therapy with etanercept: a recombinant fusion anti-cytokine treatment for rheumatoid arthritis.

Etanercept (Enbrel; Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand-binding domain of the 75 kD receptor for tumor necrosis factor-alpha (anti-TNFalpha) and the Fc portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti-TNFalpha therapy on human reproductive function or its use before ovulation induction. As TNFalpha potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFalpha-inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic ( > 1 year) pre-ovulatory TNFalpha-inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.

Adult↗
PubMed1985

[Ovulation induction in sterile females with the polycystic ovary syndrome].

The outcomes of ovulation induction in 34 infertile women with polycystic gonads were presented. The ovulation was inducted by the ovarian wedge resection or conservative treatment with either clomiphen alone or in association with human chorionic gonadotropin (HCG). The procedure of choice of specific method of management was dependent on the results of laparoscopy, while an ovarian biopsy was performed and histopathological evaluation of segments. In patients with insignificantly enlarged ovarian tunica albuginea conservative treatment with hormones was carried out, in patients with either marked enlarged tunica albuginea or thecal cells in stroma ovarian wedge resection was performed. The presented method of management caused the ovulatory cycles in 85.2% of cases and pregnancies in 61.7% of cases.

Adult↗
PubMed1996

The effect of elevated serum progesterone during ovulation induction in in vitro fertilization-embryo transfer.

OBJECTIVE: Our purpose was to determine whether elevated progesterone (P) during ovulation induction in IVF-ET cycles is a poor prognostic factor for achieving pregnancy. DESIGN: We retrospectively reviewed 672 consecutive IVF-ET cycles in which ovulation was performed using luteal LA downregulation and hMG. SETTING: The ART program at the Brigham & Women's Hospital, a tertiary care institution, was the study setting. MAIN OUTCOME MEASURES: Patients were divided into groups by serum P levels at baseline, on stimulation day 5, on the day of hCG injection, and, on the day after hCG injection and the following parameters were compared: duration of luteal LA treatment, number of ampoules of hMG used, estradiol (E2) levels, number of follicles > or = 12 mm, number of follicles > or = 15 mm, number of oocytes, number of normal embryos, number of polyspermic embryos, fertilization rate, implantation rate, and clinical and ongoing/live birth pregnancy rates. RESULTS: Based on serum P level, patients were divided into three groups: Group I, < or = 0.31 ng/ml (conversion factor to SIU, 3.180); Group II, and > 0.3 and < 1.0 ng/ml and Group III, > or = 1.0 ng/ml. Measureable P at baseline was associated with a higher cancellation rate, but no difference in other cycle outcome parameters. Progesterone > 0.31 ng/ml on stimulation day 5 was associated with a higher fertilization rate in Groups II and III, but there was no difference in the clinical pregnancy or ongoing/live birth rates among the three groups. Based on P on the day of hCG administration, Groups II and III had significantly more oocytes and higher fertilization rates than did Group I, however, clinical pregnancy and ongoing/live birth rates were not significantly different. On the day after hCG, there was a trend toward a higher clinical pregnancy rate in Group III, which had younger patients, better follicular recruitment, and more embryos than Groups I or II, but these differences did not reach statistical significance. CONCLUSIONS: Serum P > 0.31 ng/ml during ovulation induction reflects good follicular recruitment, and is not a predictor of IVF outcome.

Adult↗
PubMed1995

Peritoneal papillary serous carcinoma arising in an infertile woman during ovulation-induction therapy: immunohistochemical expression of LH/hCG receptors.

A case of peritoneal papillary serous carcinoma arising in an infertile patient during ovulation-induction therapy is presented. A 34-year-old woman with past history of ovulation-induction therapy for infertility again received fertility drugs. During the use of gonadotropic hormones, massive ascites developed and an exploratory laparotomy revealed serous papillary carcinoma on the surface of bilateral ovaries, pelvic peritoneum, and omentum. Immunohistochemical analysis showed the tumor cells to be positive for luteinizing hormone/human chorionic gonadotropin receptors and negative for sex steroid receptors. A possible relationship between the use of gonadotropic hormones and cancer development is discussed.

Adult↗
PubMed1989

Clinical characteristics of ovulation induction with human menopausal gonadotropins with and without leuprolide acetate in polycystic ovary syndrome.

Ovulation induction in polycystic ovary syndrome (PCOS) with human menopausal gonadotropins (hMG) results in suboptimal cycle fecundity and frequently is complicated by ovarian hyperstimulation. The use of a gonadotropin releasing-hormone agonist (Gn-RH-a) with hMG induction of ovulation may improve the therapeutic outcome. In this prospective, randomized trial, 27 women with PCOS underwent a total of 25 cycles of hMG alone and 33 cycles with adjunctive GnRH-a (leuprolide) treatment. Premature luteinization was seen less frequently in the leuprolide-treated cycles than in cycles treated with hMG alone. There were no differences between the treatments in ovarian sensitivity to hMG. Cycle fecundity was 0.16 for hMG alone cycles, and 0.27 for leuprolide with hMG cycles, which were not statistically different. We conclude that the sensitivity of the PCOS ovary to hMG is not affected by 4 weeks of leuprolide pretreatment.

Drug Therapy, Combination↗
PubMed1987

Mild to moderate abnormalities of semen do not affect pregnancy rates during ovulation induction with gonadotrophins.

One or more semen analysis results were available for 195 men whose wives responded to ovulation induction with gonadotrophins performed at The Royal Women's Hospital since 1963. Fifty-three men (27%) has subnormal semen analyses by conventional criteria: sperm concentration less than or equal to 20 X 10(6)/ml, motility less than or equal to 40% or normal morphology less than or equal to 50%. The lifetable pregnancy rates were not significantly different for those with subnormal and normal semen (chi 2 = 0.169), by six cycles 64% (s.e.m. = 7) with subnormal semen had conceived compared with 59% (s.e.m. = 5) with normal semen. It appears that lower limits of semen quality could be relaxed for women needing ovulation induction with gonadotrophins.

Female↗
PubMed1994

Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization.

OBJECTIVE: To determine if women who previously had demonstrated poor ovarian responsiveness during ovulation induction for IVF would obtain an improved follicular response by the administration of microdoses of GnRH agonist (GnRH-a). DESIGN: Prospective evaluation using the same patients' previous assisted reproductive technology cycles as historic controls. SETTING: Large military tertiary care center. PATIENTS: Thirty four patients who were low responders (peak E2 < 500 pg/mL [conversion factor to SI unit, 3.67]) during ovulation induction with luteal phase GnRH-a suppression followed by exogenous gonadotropins. INTERVENTIONS: Follicular phase administration of 20 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and supplemented with exogenous gonadotropins beginning on cycle day 5. MAIN OUTCOME MEASURES: Paired analysis of initial E2 response, peak E2 level attained, number of follicles > or = 16 mm, duration of stimulation, ampules of gonadotropins required, late follicular LH levels, number of mature oocytes retrieved, and fertilization rates. RESULTS: Ovarian responsiveness was enhanced during the microdose GnRH-a stimulation cycle when compared with the previous stimulation cycle. Specifically, the patients had a more rapid rise in E2 levels, much higher peak E2 levels, the development of more mature follicles, and the recovery of larger numbers of mature oocytes at the time of retrieval. None of the patients had premature LH surges as evidenced by a significant rise in LH levels or a significant decline in E2 levels. There were no differences in the fertilization rates. CONCLUSION: Microdose GnRH-a administration beginning in the early follicular phase may result in an augmented ovarian response when compared with traditional GnRH-a-exogenous gonadotropin stimulations. Additionally, it may decrease gonadotropin requirements while effectively preventing premature LH surges.

Adult↗
PubMed1994

Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin.

A total of 114 patients admitted to an in-vitro fertilization-embryo transfer programme for the first time, were randomly assigned to the study group or controls. Gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal gonadotrophin (HMG) were used for ovulation induction. The study patients were followed up merely by ultrasonography and the controls by ultrasonography and serum determinations of oestradiol, progesterone and luteinizing hormone (LH). There was no significant difference in the duration and total amount of HMG used for ovulation induction (10.9 versus 11.5 days and 34.8 versus 37.9 ampoules, respectively). The number of oocytes retrieved (11.7 versus 13.4) and the numbers of embryos replaced (2.6 versus 2.8) and cryopreserved (1.9 versus 3.3) were also similar. Pregnancy rates were similar. Pregnancy rate per ovum retrieval was 22.2 versus 25% and per embryo transfer 27.2 versus 26.5%. Oestradiol patterns were also similar. The rate and severity of ovarian hyperstimulation syndrome were virtually identical. We conclude that 'ultrasound-only' monitoring of ovulation induction in IVF cycles treated by GnRHa-HMG in the long protocol is as effective and safe as the conventional ultrasound and hormone determination, but far simpler, swifter and more cost-effective.

Adult↗