Hysterosalpingography prior to the gonadotropin stimulated intrauterine insemination improves clinical pregnancy rates in women with unexplained infertility.

PURPOSE OF INVESTIGATION: Gonadotropin stimulated intrauterine insemination (IUI) cycles performed following one month after hysterosalpingography (HSG) are associated with improvement in clinical pregnancy rates in unexplained infertile couples. MATERIALS AND METHODS: A retrospective cohort study was performed between 2008 and 2014. A total of 92 unexplained infertile couples undergoing their first cycle IUI stimulated by gonadotropins were included in the analysis. Participants were classified into two groups according to IUI cycles performed one month (Group A, n = 25 cycles) or longer than one month (Group B, n = 67 cycles) after the HSG procedure. RESULT: The overall clinical pregnancy rate was found as 25% (23 clinical pregnancies / 92 cycles). Clinical pregnancy rate was 44 % (11/25) for Group A and 17.9 % (12/67) for Group B. In Group A, there were significantly higher clinical pregnancy rates compared to Group B (OR: 3.6, 95% CI, 1.3-9.8; p = 0.012). CONCLUSIONS: It has been demonstrated that fertility improving effect of HSG was most prominent in the first six months after procedure. Likewise, in gonadotropin stimulated IUI cycles performed following one month after HSG, there seems to be an improvement in pregnancy rates in unexplained couples. In unexplained cases, it may be a reasonable approach to plan IUI cycles in the first month after HSG in clinical practice.

In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome.

OBJECTIVE: To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS. DESIGN: Prospective observational study. SETTING: University fertility clinic. PATIENT(S): One hundred forty-four women undergoing 180 in vitro oocyte maturation treatment cycles. INTERVENTION(S): Transvaginal immature oocyte recovery from unstimulated ovaries 36 hours after hCG priming. In vitro oocyte maturation and fertilization. Fresh embryo transfer. MAIN OUTCOME MEASURE(S): Immature oocytes collected, metaphase II oocytes, and embryos produced. Implantation and pregnancy rates. RESULT(S): The overall oocyte maturation and fertilization rates attained were 80.3% (1,222 of 1,522) and 76.5% (935 of 1,222), respectively. Significantly fewer immature oocytes were retrieved from normal ovaries (5.1 +/- 3.7) compared with the PCO (10.0 +/- 5.1) or PCOS (11.3 +/- 9.0) groups. Fertilization and cleavage rates were comparable among the three groups. The implantation, pregnancy, and live birth rates per transfer for normal ovaries were 1.5%, 4.0%, and 2.0%, respectively; for PCOs 8.9%, 23.1%, 17.3%, respectively; and for women with PCOS 9.6%, 29.9%, and 14.9%, respectively. CONCLUSION(S): Immature oocytes retrieved from normal ovaries, PCOs, or women with PCOS, when using hCG priming before oocyte retrieval, have a similarly high maturation, fertilization, and cleavage potential. In vitro maturation is a useful treatment option, particularly for women with PCOs.

Pregnancy and delivery after cryopreservation of zygotes produced by in-vitro matured oocytes retrieved from a woman with polycystic ovarian syndrome.

This case report describes the birth of a healthy infant after cryopreservation of zygotes produced by in-vitro matured oocytes retrieved from an anovulatory woman with polycystic ovarian syndrome (PCOS). To initiate the treatment cycle, the patient received intravaginal progesterone at night for 10 days to induce a withdrawal bleed. Oocyte retrieval was performed on day 11 following a withdrawal bleed. The patient was administered 10,000 IU of HCG subcutaneously 36 h prior to oocyte collection. A total of 63 immature oocytes were obtained; 10 were morphologically abnormal. Following incubation for 24--48 h in the maturation medium, TC-199 supplemented with 20% patient's own serum, 75 mIU/ml FSH and LH, 77.4% (41/53) of the oocytes were at the metaphase-II stage. Thirty-one (31/41, 75.6%) were fertilized using ICSI with her husband's spermatozoa, 15 fertilized oocytes were cultured for embryo transfer and 16 were frozen at the pronuclear stage. Pregnancy ensued following fresh embryo transfer. Unfortunately, the pregnancy was miscarried eight weeks later. However, the second frozen-thawed embryo transfer attempt resulted in a full-term pregnancy with delivery of a healthy male infant.

Bone density in a population of long term oral contraceptive pill users does not differ from that in menstruating women.

Prevention of osteoporosis is a major public health issue. Amenorrhoeic women have lower bone density than normally menstruating women, which is related to the duration of amenorrhoea and the severity of oestrogen deficiency. Bone mineral density (BMD) in amenorrhoeic women can be improved by oestrogen replacement in the form of the combined oral contraceptive pill (COCP), so increased BMD might be an important non-contraceptive benefit of the COCP in menstruating women. Previous studies have been variably reported, but have used different methodologies for measurement of BMD. We measured BMD using the DEXA technique in long term COCP users and compared this with menstruating women who had never used the COCP. No differences in bone density were found, suggesting that the COCP does not improve bone mass in menstruating women who are adequately oestrogenised by their own ovaries.

Accuracy of ovarian reserve tests.

Several tests predict ovarian reserve in women undergoing assisted reproductive technologies. However, the accuracy of these tests in assessing the number of the remaining follicles within the ovary (ovarian reserve) has not been previously validated. The aim of this study was to assess the accuracy of ovarian reserve tests, namely basal and clomiphene-stimulated follicle stimulating hormone (FSH) concentrations and gonadotrophin-releasing hormone (GnRH) agonist stimulation test in predicting the number of the follicles within the ovaries. The ovaries of 22 parous women over 35 years of age who underwent oophorectomy were examined histologically for follicle number. Early follicular phase serum FSH, clomiphene citrate challenge tests (CCCT) and GnRH agonist stimulation test (GAST) were performed in the menstrual cycle prior to the surgery. The predictive value of these tests was then assessed. A positive correlation was detected between basal serum oestradiol concentrations and follicles per unit tissue but no significant correlation was detected between basal and clomiphene-stimulated FSH and follicles per unit tissue. The receiver operator characteristic curves indicated that the clomiphene citrate challenge test was the most accurate of the three tests assessed. In conclusion, none of the tests in this study accurately reflects ovarian reserve.

Endocrinological and clinical analysis of hyperprolactinemic patients with and without ultrasonically diagnosed polycystic ovarian changes.

In the present study we aimed to identify the relationship of hyperprolactinemia and polycystic ovarian changes. We retrospectively analyzed the endocrinological and clinical features of 79 hyperprolactinemic patients detected during a 3-year period ending in March 1995. Patients who had hypothyroidism, macroprolactinoma and drug-induced hyperprolactinemia were excluded from the study. Among 61 hyperprolactinemic patients, 41 (67.2%) had ultrasonographically diagnosed polycystic ovaries (PCO). Prolactin levels in the PCO and non-PCO groups were 32.8 +/- 5.8 and 36.7 +/- 5.1 ng/dl, respectively, which was a significant difference (p < 0.05). Hirsutism was associated with hyperprolactinemia in 55.7% of the patients and was found to be more frequent in the PCO (58.8%) than the non-PCO group (41.2%). The mean Ferriman Gallwey scores and both total and free testosterone levels were significantly higher in the PCO group in comparison to the non-PCO group. In addition, a significantly higher body mass index was detected in patients with PCO. We documented a frequent association between hyperprolactinemia and polycystic ovarian changes and suggested that hyperprolactinemia in PCO is most likely related to a pathologic-endocrinologic milieu.

Intravenous albumin prevents moderate-severe ovarian hyperstimulation in in-vitro fertilization patients: a prospective, randomized and controlled study.

OBJECTIVE: To assess the effectiveness of intravenous administration of albumin in prevention of ovarian hyperstimulation syndrome (OHSS) in patients of an in-vitro fertilization program. STUDY DESIGN: Prospective randomized study. Patients with hCG day E2 levels are 11010 pmol/l (3000 pg/ml) or more were recruited into two groups. Group A (n = 27) received 10 g 20%, 50 ml human albumin infusion before oocyte pick-up and no medication was administered in Group B (n = 28). RESULTS: Patients were similar in terms of cycle characteristics. No moderate-severe OHSS developed in Group A whereas one severe OHSS case and four moderate OHSS cases developed in Group B. Statistical analysis revealed a significant (P < 0.05) protection in albumin treated group. CONCLUSION: Human albumin proves effectiveness in prevention of moderate-severe OHSS.

Estrogen deprivation, rather than age, is responsible for the poor lipid profile and carbohydrate metabolism in women.

UNLABELLED: The protective effect of estrogen against cardiovascular diseases (CVD) in women disappears after menopause. However, it is not clear whether the change in risk factors after menopause is related to aging or estrogen deprivation. OBJECTIVE: To assess the risks for CVD and the contribution of aging in estrogen-deprived women. METHODS: Forty-one patients with premature ovarian failure (POF) (group 1) and 30 patients with natural menopause (group 2) were investigated with respect to well-known risk factors for CVD. Fifteen young women at reproductive age (group 3) were taken as controls. The median ages (ranges) of the groups were 31 (19-40), 52 (46-67) and 26 (24-29) years, respectively. Family and personal history for CVD, smoking, oral contraceptive usage, physical examination, blood pressure measurement, body mass index (BMI), blood level of fasting insulin, diabetes mellitus, and the levels of lipoprotein proteins were the examined parameters regarding the risks for CVD. RESULTS: The levels of triglycerides and very low density lipoprotein (VLDL) cholesterol were not different in the 3 groups. The levels of fasting insulin (11.3 +/- 6.6 vs. 10.2 +/- 5.8 IU/ml), the ratio of fasting insulin to fasting blood glucose (12.2 +/- 6.3% vs. 10.5 +/- 5.4%), high density lipoprotein (HDL) cholesterol (51.9 +/- 12.9 vs. 51.6 +/- 9.7 mg/d), low density lipoprotein (LDL) cholesterol (113 +/- 47 vs. 127 +/- 37 mg/dl) and the ratio of HDL to total cholesterol (27.2 +/- 9.8% vs. 24.1 +/- 6.9%) were not different in women with POF and natural menopause. These parameters were all better in controls with respect to risk for CVD (respectively, 6.5 +/- 2.0 IU/ml, 7.4 +/- 2.2%, 37.9 +/- 5.3 mg/dl, 80 +/- 40 mg/dl, P < 0.05). CONCLUSION: Risk factors for CVD are related to estrogen deprivation. Aging does not have an important impact on CVD within the age range of this study group.

Comparison of four different treatment regimes in hirsutism related to polycystic ovary syndrome.

Polycystic ovary syndrome is the most common endocrinological problem associated with hirsutism. The objective of this study was to compare four different treatment modalities for hirsutism related to this syndrome. Pelvic ultrasonography was performed on all patients who were referred to our Reproductive Endocrinology Outpatient Clinic because of complaints of hirsutism. After exclusion of hyperandrogenism caused by endocrine abnormalities other than polycystic ovary syndrome, 141 patients were included in the study. Patients were divided into four groups in regard to the drug chosen for treatment. Group 1 (n = 48) received low-dose combined oral contraceptive. Group 2 (n = 65) was treated with cyproterone acetate 100 mg daily for the first 10 days of a 21-day cycle with an oral contraceptive containing 2 mg cyproterone acetate, Group 3 (n = 12) with spironolactone (100-200 mg daily) and Group 4 (n = 16) with ketoconazole (400 mg daily). All patients were followed frequently with respect to side-effects, hirsutism scoring, and lipid and hormonal levels. All four drug regimens were effective in the treatment of hirsutism related to polycystic ovary syndrome, but the most effective seemed to be ketoconazole. The decrement level in hirsutism scoring was the largest in the ketoconazole group, followed by the cyproterone, oral contraceptive and spironolactone groups (34.6 +/- 2.2%, 20.1 +/- 2.7%, 18.1 +/- 2.7% and 12.8 +/- 3.7%, respectively, p < 0.05). Although high-density lipoprotein-cholesterol levels increased in all groups, this increment was smaller in Group 4 than in Groups 1 and 2 (5.1 +/- 2.8%, 34.1 +/- 5.5% and 29.1 +/- 4.9%, respectively, p < 0.05), but not statistically different from that in Group 3 (22.3 +/- 5.9%). The free testosterone levels decreased after treatment in all groups, but the decrement ratios did not differ significantly among groups, although the decrease in free testosterone levels with treatment seemed to be higher in the ketoconazole group than in Groups 1, 2 and 3 (57.0 +/- 2.5%, 22.7 +/- 10.2%, 26.7 +/- 6.5% and 9.5 +/- 19.9%, respectively). In conclusion, ketoconazole seems to be an excellent alternative to more-recognized therapies, but its effect on lipoprotein profile requires further study, because the hyperandrogenism, and the other problems related to hyperandrogenism besides hirsutism, should also be treated.

Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea.

OBJECTIVE: Osteopenia in Turner's syndrome is well recognized. This study is aimed to elucidate whether this is an intrinsic feature of the disorder, or is a non-specific feature resulting from oestrogen deficiency. DESIGN: Comparison of bone mineral density and fracture rate in Turner's patients and in 46,XX women with equivalent oestrogen deprivation from other causes. SUBJECTS: One hundred and twenty women in the reproductive age range (16-45 years): 40 with Turner's syndrome, 40 with other forms of primary amenorrhoea, and 40 healthy controls matched to patients for duration of oestrogen usage. MEASUREMENTS: Measurement of bone mineral density in the lumbar spine (and femoral neck in some subjects) by dual-energy X-ray absorptiometry, and reported history of fracture. RESULTS: Vertebral bone mineral density was similar in women with Turner's syndrome (mean 0.84, SD 0.11 g/cm2) and those with other causes of primary amenorrhoea (mean 0.81, SD 0.11 g/cm2; P = 0.26). Both groups had severe osteopenia compared with healthy controls (mean 1.06, SD 0.09 g/cm2, P < 0.0005, confirmed after correction for height and weight). Fractures had been sustained by 45% (10/22) of Turner's patients for whom information was available, a high frequency compared with controls (P = 0.014); half of these were at 'osteoporotic' sites of fracture (wrist, vertebra, femoral neck). CONCLUSION: Osteopenia in Turner's syndrome is not an intrinsic feature specific to this disorder, but results from extreme oestrogen deprivation. Early treatment with oestrogen is therefore recommended.

Do the suppression criteria in GnRH-a cycles predict in vitro fertilization outcome?

The addition of gonadotropin releasing hormone analog (GnRH-a) to controlled ovarian hyperstimulation regimes has been reported to have several advantages, such as reduced cancellation rate, fewer premature luteinizations and increased clinical pregnancy rate. The aim of this study was to determine the effect of pituitary/ovarian suppression, in terms of the levels of luteinizing hormone (LH), estradiol and follicle stimulating hormone (FSH), and the duration of GnRH-a administration, on in vitro fertilization (IVF) outcome. Retrospectively, 153 IVF cycles with GnRH-a and human menopausal gonadotropin (hMG) were examined. After a minimum of 10 days of GnRH-a administration, the patients were started on hMG. The correlations were investigated between the fertilization rates, the numbers of retrieved oocytes and transferred embryos, the cancellation rates, the suppressed LH, FSH and estradiol levels, the total ampules of hMG used and the duration of GnRH-a usage. The duration of GnRH-a usage and the total ampules of hMG used were not correlated. The number of oocytes retrieved and total number of hMG ampules used showed weak correlations with suppressed levels of FSH (-0.297 and 0.285, respectively). However, the fertilization, cleavage and pregnancy rates did not correlate with the LH, FSH and estradiol levels on hMG start days. In conclusion, for selected cases, 10 days of GnRH-a administration is sufficient to suppress endogenous gonadotropin levels. Since FSH and LH are protein hormones and their bioactivity may change in a manner that is unrelated to their immunological levels, it is not necessary to measure FSH, LH and estradiol levels to detect whether suppression is adequate.

Effect of treatment on established osteoporosis in young women with amenorrhoea.

BACKGROUND AND OBJECTIVE: Amenorrhoea in women of reproductive age causes loss of bone mineral. This study assessed the effect of treatment of amenorrhoea on bone mineral density. DESIGN: Serial measurements of bone mineral density were obtained in women receiving treatment for amenorrhoea. PATIENTS: Eighty-five women aged 17-40 with a past or current history of amenorrhoea, from various causes, with median duration of 46.5 months (range 8 months-21 years). MEASUREMENTS: Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry. RESULTS: Initial vertebral bone mineral density was low, mean 0.85 (SD 0.10) g/cm2. After an interval of 19.6 (SD 7.5) months on treatment there was a highly significant increase to 0.89 (SD 0.10) g/cm2 (P < 0.0005). This was equivalent to a gain in bone mass of 2.1% per year (95% confidence interval 1.5-2.8%). Improvement was seen in all diagnostic groups (except polycystic ovary syndrome) and with all types of therapy. We observed no difference in the response of previously untreated patients compared with those already on treatment, nor any change in response with increasing duration of treatment. No new fractures were reported during the study. CONCLUSIONS: Bone mineral density in young women with amenorrhoea is improved by appropriate treatment, but recovery is not substantial. Hence early diagnosis and therapy is essential to prevent bone loss.

Lipid profiles in women with hirsutism and polycystic ovaries.

We examined the correlation between hyperandrogenemia and lipid profiles in 25 hirsute patients with polycystic ovary syndrome in our reproductive endocrinology outpatient clinic. Concentrations of triglycerides, low density lipoprotein cholesterol and total cholesterol were increased and concentrations of high density lipoprotein (HDL) cholesterol were decreased in women with severe hirsutism. Total and free testosterone levels were correlated with triglycerides (r = 0.72, p < 0.05; r = 0.55, p < 0.01, respectively) and HDL cholesterol (r = -0.55; p < 0.05; r = -0.68, p < 0.05, respectively). There was no correlation between levels of androstenedione, dehydroepiandrosterone sulfate or 17-OH progesterone and any parameters of the lipid profiles. In those with a luteinizing hormone/follicle stimulating hormone ratio > or = 1.5, total testosterone levels were higher than in those with a lower ratio (129.5 +/- 6.4 vs. 95.2 +/- 9.2 ng/dl, p < 0.05), HDL cholesterol levels were lower (45.2 +/- 4.2 vs. 60.4 +/- 4.8 mg/dl, p < 0.05) and triglyceride levels were higher (138.1 +/- 4.5 vs. 92.6 +/- 6.1 mg/dl, p < 0.001). We conclude that altered lipid profiles in women with hirsutism are a result of high testosterone levels.

Endocrinological, ultrasonographic and clinical findings in adolescent and adult polycystic ovary patients: a comparative study.

This study was performed to compare clinical and endocrine features and ultrasonographic data of adolescent (< or = 18 years old) and adult (> or = 19 years old) patients with ultrasound-diagnosed polycystic ovaries (PCOs) in our Reproductive Endocrinology outpatient clinic. The adolescent group included 35 PCO patients while 125 were in the adult group. Hirsutism was present in 64.7% of the adolescent group and in 49.6% of the adult group. Menstrual irregularities were detected as oligomenorrhea (42.8%), amenorrhea (20%) and irregular but normal cycles (17.4%) in the adolescent group; the figures for the adult group were 46.4, 8.8 and 23.2%, respectively. These differences were not statistically significant. The mean body mass index of the adult PCO group was significantly higher than the adolescent PCO group (p < 0.05). The endocrine features (estradiol, follicle stimulating hormone, luteinizing hormone (LH), prolactin, total testosterone, free testosterone, 17-OH progesterone, androstenedione, thyroid stimulating hormone, dehydroepiandrosterone sulfate (DHEAS)) and the ovarian volume of both groups were comparable. There was a significant positive correlation between ovarian volume and serum LH, total testosterone, free testosterone, androstenedione and DHEAS in both groups. We conclude that polycystic ovarian syndrome is a disorder with perimenarchal onset, the clinical, endocrine and ultrasound features of which will not change by age, although patients are prone to gain weight as they get older.

Tamoxifen: an alternative approach in clomiphene resistant polycystic ovarian syndrome patients.

Twenty patients with ultrasound diagnosed polycystic ovaries and high luteinizing hormone levels who failed to respond to clomiphene citrate were given tamoxifen to induce ovulation. Tamoxifen 20 mg daily (group 1, n = 10) and 40 mg daily (group 2, n = 10) was given for 5 consecutive days from the third to seventh day of the cycle. Treatment was monitored by serial ultrasound scans and assessment of serum estradiol. Human chorionic gonadotrophin (hCG) was administered when at least one follicle was > 16mm and serum estradiol level was > 300 pg/ml per follicle. Ovulation was confirmed with detection of the follicular rupture ultrasonographically 2 days after hCG and midluteal progesterone levels. The ovulation rate achieved in group 2 patients was significantly higher (p = 0.01) than group 1. Three pregnancies were achieved in group 2 patients while there was no pregnancy in group 1. The only side effect was ovarian cyst formation in one patient in group 1. As a result, tamoxifen might be a good choice for clomiphene resistant patients prior to treatment with surgery or hMG.

Clinical and endocrine features of ultrasound diagnosed polycystic ovary patients: the correlation between ovarian volume and androgen activity.

One hundred and twenty five patients with polycystic ovaries on ultrasonography and 17 controls with normal ovaries on ultrasound and regular ovulary cycles underwent clinical and endocrine evaluation. Of 125 ultrasound-diagnosed polycystic ovary patients (PCO) 49.6% complained about hirsutism, 55.2% had menstrual disturbances (46.4% oligomenorrhea, 8.8% amenorrhea), 23.2% had normal but irregular cycles and 50.4% had infertility. PCO patients had significantly higher mean serum LH, testosterone, androstenedione and DHEAS levels and higher mean ovarian volume compared with the control group. Sixty seven percent of PCO patients had enlarged ovaries and significantly higher mean serum LH, testosterone, androstenedione and DHEAS levels, compared with the PCO patients who had ovarian volume within normal range. There was a significant positive correlation between ovarian volume and serum LH, testosterone, androstenedione, DHEAS levels. Hirsutism, oligomenorrhea, irregular cycles were equally present in patients with normal ovarian volume and enlarged ovaries. These results illustrate the importance of ovarian volume measurement as an indicator of androgen production in PCO patients.