Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of aromatase inhibitor vs. gonadotrophin-releasing hormone agonists in treating premenopausal women with uterine adenomyosis. DESIGN: A prospective randomized controlled study. SETTING: A university hospital and a private practice setting. POPULATION: Thirty-two patients with uterine adenomyosis. METHODS: Patients were randomly allocated to receive oral letrozole (2.5 mg/day) or a subcutaneous gonadotropin-releasing hormone agonist (goserelin, 3.6 mg) for 12 weeks. Uterine and adenomyoma volumes were determined at baseline and during treatment at four, eight and 12 weeks. OUTCOME MEASURES: Measurements were performed at baseline and during treatment at four, eight 8 and 12 weeks, and mean values were calculated. Symptoms at the start and after 12 weeks were evaluated. RESULTS: No significant differences in the total uterine size between the post treatment uterine volumes in the two groups (20.1, 15.4 and 13.0 cm(3) vs. 21.7, 15.1 and 11.7 cm(3) , at four, eight and 12 weeks, respectively). Total adenomyoma volume decreased by 8.6, 29.7 and 40.9% vs. 5.7, 34.6 and 49.1% after four, eight and 12 weeks of treatment, in group A and B, respectively. Two patients became pregnant in group A during treatment. CONCLUSIONS: Aromatase inhibitors are as effective as gonadotropin-releasing hormone agonists in reducing adenomyoma volume and improving symptoms.

Progesterone rise on the day of HCG administration (premature luteinization) in IVF: an overdue update.

Premature luteinization (PL) refers to a rise in serum progesterone (P) levels on the day of hCG administration. Most studies used an absolute P level on the day of hCG administration as an indicator of PL, and the cutoff level differed from 0.8 to 2 ng/mL. Some authors defined PL as a P/E2 ratio of >1. There is a marked variation in the incidence (13% to 71%), of PL due to discrepancies in definition, population characteristics and/or treatment protocols. The pathogenesis of PL in COH is still poorly understood. Several hypotheses may be considered to explain this phenomenon: elevation of follicular LH levels, serum accumulation of HCG from HMG, increased LH receptor sensitivity of the granulosa cells to FSH, or poor ovarian response with increased LH sensitivity. The consequences of this premature elevation of serum P on IVF outcome remain controversial. Attempts to prevent COH include: use of Low-dose hCG alone in the late COH stages, flexible antagonist protocol, use of mifepristone, aspiration of a single leading follicle, hCG administration when the levels of serum P exceeded 1.0 ng/mL.

Evaluation of a single-step diagnosis and treatment of premalignant cervical lesion by LEEP.

OBJECTIVE: To explore whether a single-step diagnosis and treatment of premalignant cervical lesions by the loop electrosurgical excision procedure (LEEP) is appropriate in women at high risk in low-resource countries. METHOD: Sixty women suspected of having a high-grade lesion on both visual inspection with acetic acid (VIA) and colposcopic examination were randomly allotted to one of 2 groups. In group 1, LEEP was performed immediately and a tissue specimen was sent for histopathologic evaluation; in group 2, a punch biopsy was performed, followed by a histopathologic evaluation; then, LEEP was performed if needed. RESULTS: Among the patients who underwent LEEP, 4 (16%) in group 1 and 3 (15.8%) in group 2 were overtreated. No patients dropped out of the study in group 1 but 5 (20.8%) did in group 2. CONCLUSION: The single-step diagnosis and LEEP treatment of premalignant cervical lesions is appropriate in low-resource countries.

Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study.

OBJECTIVE: To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not. DESIGN: Prospective randomized controlled study. SETTING: Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt. PATIENT(S): Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out. MAIN OUTCOME MEASURE(S): Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment. RESULT(S): In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels. CONCLUSION(S): GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.

Effect of sperm morphology and number on success of intrauterine insemination.

OBJECTIVE: To assess the effects of the number of motile spermatozoa inseminated and percentage of morphologically normal spermatozoa on the success of IUI. DESIGN: A prospective observational study. SETTING: University teaching hospital and private practice setting. PATIENT(S): The study comprised 393 couples who underwent 714 IUI cycles. INTERVENTION(S): All IUI cycles were preceded by ovarian superovulation with clomiphene citrate 50 mg tablets orally twice daily for 5 days starting on the second day of menses and one hMG ampule 75 IU IM daily for 5 days starting day 5 of the cycle. Cycles were monitored by transvaginal ultrasound. The IUI was performed with a catheter 36 +/- 4 hours after hCG injection. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): A total of 79 clinical pregnancies were obtained, for a pregnancy rate per cycle of 11.06%. The pregnancy rate per cycle was 5.55% when the number of motile spermatozoa was <5 x 10(6) and 24.28% with normal motile sperm >5 x 10(6). For patients <25 years old, with number of motile spermatozoa >5 x 10(6), the pregnancy rate per cycle was 28.2%, which is significantly higher than that of other age groups. Above the age of 35 years, no pregnancies were reported with number of motile spermatozoa <5 x 10(6), and the pregnancy rate was very low (0.84%) with number of motile spermatozoa >5 x 10(6). When the normal sperm morphology was >30% and number of motile spermatozoa inseminated >5 x 10(6), the pregnancy rate was 20.77%. CONCLUSION(S): Intrauterine insemination used for treating male factor infertility has little chance of success when the woman is older than 35 years, the number of motile spermatozoa inseminated is <5 x 10(6), or normal sperm morphology is <30%.

N-acetyl cysteine vs. metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study.

OBJECTIVE: To compare the effect of N-acetyl cysteine and metformin on hormonal profile (insulin and T) and ovulation rate in women with clomiphene citrate-resistant polycystic ovary syndrome. DESIGN: Prospective randomized controlled study. SETTING: Department of obstetrics and gynecology in a university hospital in Egypt. PATIENT(S): Sixty-one infertile women with clomiphene citrate-resistant polycystic ovary syndrome were assigned randomly to receive either metformin (1,500 mg/d) or N-acetyl cysteine (1.8 g/d) for 6 weeks. INTERVENTION(S): Hormonal profile was determined before and after the course of treatment. Folliculometry was performed to assess ovulation. MAIN OUTCOME MEASURE(S): Ovulation rate and insulin and T changes. RESULT(S): In the metformin group, there was a significant decrease in the fasting glucose, fasting insulin, and total T. In the N-acetyl cysteine group, there was no significant difference in the fasting glucose or fasting insulin and there was a significant decrease in total T. There was no significant difference in the fasting glucose-fasting insulin ratio in both groups. In the metformin group, the rate of ovulation was 51.6% (16/31), vs. 6.7% (2/30) in the N-acetyl cysteine group, which was statistically significant. CONCLUSION(S): Metformin alone is an effective drug in inducing ovulation in clomiphene citrate-resistant polycystic ovary syndrome, whereas N-acetyl cysteine alone is not. Further large studies are required to confirm our results.

Letrozole induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio.

Letrozole induction of ovulation in clomiphene citrate-resistant women with polycystic ovary syndrome is associated with an ovulation rate of 54.6% and pregnancy rate of 25%. There was no significant difference between letrozole responders and nonresponders in age, period of infertility, body mass index, waist circumference, LH, FSH, or LH/FSH ratio.

Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study.

BACKGROUND: The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation. METHODS: Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised. RESULTS: There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism. CONCLUSION: Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.