Pathogenesis of polycystic ovary syndrome--the enigma unravels?
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Biomedical subjects
Publications and source records attributed to A Balen.
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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.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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The overall incidence of clinically important (moderate to severe) OHSS ranges from 1% to 10% of IVF cycles, but only a small proportion (0.5% to 2%) of the cases are severe. In extreme but rare cases, secondary complications such as deep vein thrombosis, respiratory distress and acute hepato-renal failure may occur. The main risk factors are the presence of polycystic ovaries, high ovarian response to superovulation therapy, the use of hCG to trigger the ovulatory process or for luteal phase support, and the endogenous production of hCG by an early pregnancy. The pathogenesis of OHSS is unknown, although the predominant biochemical mediator is thought to be the renin-angiotensin system. Ovarian stimulation should always be carefully monitored to identify those women at risk. In IVF cycles, the hCG injection should be withheld if the risk is judged to be too great. Some women will benefit from a policy of proceeding to collect oocytes, but electively cryopreserving any resulting embryos, thus allowing the ovarian stimulation cycle not to be wasted. The administration of albumin at the time of oocyte collection will reduce the chance of severe OHSS occurring. If a decision is made to proceed with oocyte recovery and embryo transfer, it may be advisable to give 5000 IU of hCG, rather than 10,000 IU, as the ovulatory trigger. Progesterone, and not hCG, should be given in the luteal phase. Women developing mild or moderate OHSS should be kept under outpatient surveillance to detect the minority that may progress to severe OHSS. Those with severe OHSS should be hospitalised for fluid and electrolyte management. Paracentesis under ultrasound guidance is recommended where there are tense ascites, but further surgical intervention should rarely be undertaken and only when there is good clinical evidence of ovarian torsion or haemorrhage.
OBJECTIVE: Our purpose was to compare cumulative conception and live-birth rates after in vitro fertilization with and without the use of the long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin. STUDY DESIGN: Life-table analysis of conception and live-birth rates in relation to ovarian stimulation regimen used in 2893 women who had one of five stimulation regimens exclusively throughout all treatment cycles, namely, human menopausal gonadotropin with or without clomiphene citrate; follicle-stimulating hormone with or without clomiphene citrate; and long, short, and ultrashort protocols of buserelin, plus follicle-stimulating hormone or human menopausal gonadotropin; and in an additional 347 women who had been administered both human menopausal gonadotropin and follicle-stimulating hormone with or without clomiphene citrate. RESULTS: The cumulative conception rate and cumulative live-birth rate were significantly higher in those women treated exclusively with the long buserelin regimen (59% and 55%, respectively, after three cycles) compared with those who only had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (39% and 29%, respectively, after three cycles) (p = 0.001 and p = 0.0001) or compared with those who had only short or ultrashort buserelin regimens (22% and 17% after two cycles) (p = 0.0001 and p = 0.005). The pregnancy failure rate in patients on the long buserelin regimen was 22.4% (95% confidence interval 14.8% to 30.0%) compared with 33.3% (95% confidence interval 29.6% to 37.0%) in those who had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (p = 0.03). When the probabilities of first conception and first live birth were examined by treatment regimen, after we allowed for the effects of age, cause of infertility, calendar year of treatment, and treatment cycle number (with a multiple logistic regression model), it was found that, relative to human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate, the odds of conceiving with the long buserelin regimen was 1.63 (95% confidence interval 1.31 to 2.03) (p < 0.001) and the odds of a live birth was 1.97 (95% confidence interval 1.53 to 2.54) (p < 0.001). Similarly, relative to short or ultrashort buserelin the odds of conceiving with long bureselin was 1.88 (95% confidence interval 1.39 to 2.55) (p < 0.001) and the odds of a live birth was 1.79 (95% confidence interval 1.25 to 2.56) (p = 0.001). CONCLUSION: Pituitary desensitization with the long protocol of buserelin significantly increases the probabilities of conception and live birth after in vitro fertilization.
OBJECTIVE: Our aim was to compare the cumulative conception and live-birth rates after in vitro fertilization in women undergoing their first course of in vitro fertilization treatment with those in women undergoing their second course of treatment, having previously achieved an in vitro fertilization pregnancy. This study occurred in a tertiary referral-assisted conception unit. STUDY DESIGN: The cumulative conception rates obtained by life-table analysis in 4115 women having their first course of in vitro fertilization therapy (7327 treatment cycles leading to 1123 pregnancies) were compared by means of the log-rank test with those of 331 women in their second course of treatment, having previously achieved an in vitro fertilization pregnancy (561 treatment cycles leading to 138 second in vitro fertilization pregnancies). Similarly, the cumulative live birth rates of 3824 women in their first course of treatment (7136 treatment cycles leading to 732 live births) were compared with those of 105 women in their second course of treatment, having previously achieved an in vitro fertilization live birth (205 treatment cycles leading to 33 second in vitro fertilization live births). RESULTS: The cumulative conception rates and cumulative live birth rates were significantly higher in women having their second course of in vitro fertilization treatment than in those having their first course (cumulative conception rate: p = 0.0001; cumulative live birth rate, p = 0.007). After five cycles of in vitro fertilization, the cumulative conception rates and cumulative live birth rates were 49.8% (95% confidence interval, 46.3% to 53.5%) and 39.0% (95% confidence interval, 35.4% to 42.9%), respectively, in those having their first course of treatment compared with 69.9% (95% confidence interval, 57.6% to 81.3%) and 68.6% (95% confidence interval, 46.1% to 88.5%), respectively, in those having their second course. The estimated median numbers of cycles taken to achieve a pregnancy and live birth (assuming all women could potentially undergo the same number of cycles) were six and eight, respectively, in the first course of treatment compared with only three and five in the second course. CONCLUSION: Women who have achieved a previous in vitro fertilization pregnancy have significantly higher cumulative conception rate and cumulative live birth rates compared with those of women having their first course of treatment.
OBJECTIVE: To compare the outcome of natural with clomiphene citrate (CC)-stimulated cycles in IVF. DESIGN: Prospective, randomized study. SETTING: Tertiary referral center for assisted conception. SUBJECTS: Thirty patients randomized to receive either no treatment (n = 14) or CC, 100 mg, from days 2 to 6 (n = 16). INTERVENTIONS: Daily ultrasound (US) scan and measurements of serum LH and E2. Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later. MAIN OUTCOME MEASURES: The number of patients reaching oocyte recovery; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorded. RESULTS: Ten cycles in the natural cycle group were abandoned before oocyte recovery compared with none in the CC group. There were significantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/- 0.2) and higher peak levels of E2 (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients treated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compared with only 4 in the natural cycle group (1 oocyte each). The oocyte recovery rate was 95%. Two patients conceived in the CC group (PR per ET, 18%) compared with none in the natural cycle group. Patients with polycystic ovaries developed more large follicles than those with normal ovaries. No patient developed ovarian hyperstimulation syndrome. CONCLUSIONS: Patients undergoing natural cycle IVF are more likely to have abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired.
The outcome of in-vitro fertilization and embryo transfer (IVF-ET) was compared in 76 patients with polycystic ovaries (PCO) diagnosed on pre-treatment ultrasound scan, and 76 control patients who had normal ovaries and were matched for age, cause of infertility and stimulation regimen. Despite receiving significantly less human menopausal gonadotrophin (HMG), patients with PCO, as compared with controls, had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration (5940 +/- 255 versus 4370 +/- 240 pmol/l, P < 0.001), developed more follicles (14.9 +/- 0.7 versus 9.8 +/- 0.6, P < 0.001) and produced more oocytes (9.3 +/- 0.6 versus 6.8 +/- 0.5, P = 0.003). However, fertilization rates were reduced in the PCO patients (52.8 +/- 3.4% versus 66.1 +/- 3.4%, P = 0.007). There was no significant difference in cleavage rates. The pregnancy rate/embryo transfer was 25.4% in the PCO group and 23.0% in the group with normal ovaries. There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries. Of the PCO patients, 10.5% developed moderate/severe ovarian hyperstimulation syndrome (OHSS) compared with none of the controls (P = 0.006). Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates. However, it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET.
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OBJECTIVE: To investigate if peritoneal oocyte and sperm transfer (POST) performed transvaginally is an effective treatment for nontubal infertility. DESIGN, SETTING, AND PATIENTS: Prospective study of 18 patients (4 with unexplained infertility, 13 with failed donor insemination, and 1 with male factor infertility) having 20 cycles of transvaginal POST in a specialist infertility unit. INTERVENTIONS: Ovarian stimulation was achieved with human menopausal gonadotropin (hMG) alone, hMG and clomiphene citrate, or gonadotropin-releasing hormone agonist with hMG. Oocyte recovery was performed transvaginally under ultrasound guidance, the pouch of Douglas rinsed repeatedly and an embryo transfer catheter used to transfer 4 x 10(6) progressively motile sperm in 1 mL and up to four oocytes into the pouch of Douglas. Luteal support was provided with human chorionic gonadotropin injections given 2 and 5 days later. RESULTS: The mean age of the patients was 32.65 +/- 5.0, and the mean length of infertility 5.07 +/- 2.32 years. The mean number of oocytes transferred was 3.53 +/- 0.87. Three pregnancies were achieved in the failed donor insemination group and 1 each in those with unexplained and male factor infertility, giving overall clinical pregnancy and live birth rates of 25% and 20% per initiated cycle. All pregnancies were achieved in those who had three or four oocytes transferred. CONCLUSION: Transvaginal POST is a useful assisted conception technique for the treatment of nontubal infertility.
OBJECTIVE: To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. INTERVENTIONS: All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14 days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n = 79) had hCG administered when the mean diameter of the largest follicle had reached 18 mm, at least two other follicles were greater than 14 mm, and serum estradiol (E2) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n = 84) and 3 (n = 84) had hCG administered 1 day and 2 days, respectively, after the above criteria had been reached. RESULTS: The mean day of hCG administration (P less than 0.01), maximum serum E2 concentration (P = 0.06), number of days of serum E2 rise (P = 0.03), and mean diameter of the largest follicle (P less than 0.0001) were significantly different. There were, however, no significant differences in the mean number of preovulatory and medium size follicles, number of oocytes recovered or embryos transferred. There were also no significant differences in the oocyte recovery, fertilization and cleavage rates, in the number of embryos frozen, or in the pregnancy rates per initiated cycle and per ET. CONCLUSIONS: There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a.
OBJECTIVE: To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS: Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS: The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS: Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.
OBJECTIVE: To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs. DESIGN: Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Nine patients with isolated hypogonadotropic hypogonadism. MAIN OUTCOME MEASURE: Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation. RESULTS: Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05). CONCLUSION: This study in isolated hypogonadotropic hypogonadism patients is consistent with the two-cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question.