Assessment of reproductive ageing patterns by hormonal and ultrasonographic ovarian reserve tests.

BACKGROUND: Tests to assess the change in ovarian reserve (OR) with age have been analysed only in monophasic or biphasic linear patterns. Our aim was to analyse an optimum curve that might define the relationship between different OR tests and age. METHODS: A total of 81 regularly menstruating women without a history of infertility were included in this prospective study. On cycle day 3, antral follicle (AF) counts, ovarian volume (OV), and serum FSH and estradiol levels were determined. Curve estimation was performed to determine the optimal relationship between age and OR tests. Optimum curves were also compared with monophasic and biphasic linear relationships. RESULTS: A quadratic model (y=a x x2+b x x+c) had the highest coefficient of determination for the AF count, OV and serum FSH level. The predictive power of this quadratic model was comparable with biphasic linear models for the OV and serum FSH level, but was better than that of the AF count. CONCLUSIONS: The pattern of reproductive ageing as assessed by hormonal and ultrasonographic OR tests does not appear to show an abrupt change at a certain age, but follows a continuously increasing rate of decline in the third decade of life. The changes in serum FSH levels and ultrasonographic OR tests follow a quadratic model in regularly menstruating women.

Mammographic density increase in women receiving different hormone replacement regimens.

OBJECTIVE: we investigated effects of different regimens of hormone replacement therapy (HRT) on mammographic density. METHODS: ninety-five postmenopausal women, who were on different HRT regimens and completed their 4-year mammographic follow-up, were included into this retrospective and comparative study. Twenty-three of these women, who had surgical menopause, received conjugated equine estrogens (CEE) (Group I) only, 26 of them received CEE and continuous medroxyprogesterone acetate (MPA) (Group II), 21 women received CEE and cyclic MPA (Group III), and the remaining 25 women received tibolone (Group IV) therapy. Before commencing on HRT, a baseline high-resolution mammography was performed, and repeated at 6-12-month intervals during the period of 4-year follow-up. All mammographies were evaluated according to the Wolfe classification. RESULTS: a diffuse increase in mammographic density was detected in five women (22%) in group I, nine women (35%) in group II, four women (19%) in group III, and two women (8%) in group IV. The increase in mammographic density was more common among women in group II than those in the other three groups. However, a statistically significant difference was found only between groups II and IV. CONCLUSIONS: different HRT regimens have different effects on breast parenchymal density on mammography. Continuous combination HRT may be more commonly associated with an increase in breast density than other forms of HRT.

Hepatic dysfunction associated with moderate ovarian hyperstimulation syndrome. A case report.

BACKGROUND: Liver dysfunction is a rare complication of severe ovarian hyperstimulation syndrome (OHSS). Based on a MEDLINE search from 1966 to September 2000, we report the second case of liver dysfunction associated with moderate OHSS. In addition, this is the first report of moderate OHSS with serum progesterone levels during the first trimester of pregnancy higher than the upper limit of normal for a third-trimester gestation. CASE: A 33-year-old nulligravida with a history of infertility had previously undergone three failed cycles of assisted reproduction. During her fourth attempt at in vitro fertilization and intracytoplasmic sperm injection, she developed moderate OHSS 11 days after embryo transfer. She was managed on an outpatient basis. Her serum progesterone and liver enzyme levels were significantly elevated, as is unusual for the moderate picture of OHSS in this patient. CONCLUSION: Hepatic dysfunction is not limited to the severe forms of OHSS. Liver function should be analyzed even in moderate cases. Further study is needed to understand the role of elevated liver function tests and serum progesterone in the pathogenesis of OHSS.

Use of third generation gonadotropin-releasing hormone antagonists in in vitro fertilization-embryo transfer: a review.

Before gonadotropin-releasing hormone agonists (GnRHa) became available, approximately 20% of stimulated cycles within an in vitro fertilization (IVF) program were cancelled due to premature LH surges. By using the GnRHa to prevent LH surges via gonadotrope GnRH receptor down-regulation and desensitization, this percentage decreased to about 2%, and concomitantly, the IVF and pregnancy rates per cycle initiated were increased. Several treatment schedules currently are in use, including the so-called "long protocol," in which the GnRHa is begun in the luteal phase and down-regulation occurs before the start of the gonadotropin-stimulation treatment phase. This is generally the most effective regimen and is presently the most frequently used protocol. However, it has some disadvantages, such as hypoestrogenic side effects and an increase in the number of ampules of FSH or hMG required for adequate stimulation. There is a new generation of GnRH antagonists now clinically available, that has been able to minimize the potential side effects and provide reliable antagonism at the GnRH receptor. These agents seem better suited than GnRHa for assisted reproductive technology (ART) cycles inasmuch as they can prevent LH surges without requiring complete gonadotropin suppression. We have reviewed the current literature concerning their use in IVF cycles.

Sperm-preparation techniques for men with normal and abnormal semen analysis. A comparison.

OBJECTIVE: To compare two commonly used sperm-preparation techniques, density gradient centrifugation and swim-up procedures, with respect to their effects on acrosome reaction (AR), hypoosmotic swelling (HOS) and nuclear maturity in men with abnormal and normal semen analyses. STUDY DESIGN: In accordance with World Health Organization criteria, 23 men with abnormal (group I) and 20 men with normal (group II) semen analyses were included in a prospective, controlled study. Each semen specimen was divided into aliquots in order to assess AR, HOS and nuclear maturity, determined with acridine orange staining, in both raw and processed semen samples using the density gradient centrifugation and swim-up techniques. RESULTS: Initial semen samples in group I revealed diminished AR, HOS and nuclear maturity rates in comparison to those in group II. In group I, density gradient centrifugation improved AR, HOS and nuclear maturity rates more than did swim-up. However, in group II it improved only the AR; HOS rates were better than with swim-up. There was a significant positive correlation between sperm concentration and HOS rate in raw semen samples from group I. In the same group, motility and morphology correlated with the nuclear maturity rate but not with AR and HOS rates. Semen samples with better motility (> 20%) or morphology (> 25%) showed better nuclear maturity rates (> 50%) in men with abnormal semen analyses. Motility had a sensitivity of 77% and specificity of 90% in predicting nuclear maturity. Morphology had similar sensitivity but lower specificity (70%). CONCLUSION: Density gradient centrifugation is superior to the swim-up technique in improving AR, HOS and nuclear maturity rates in men with abnormal semen analyses. However, when only nuclear maturity rate is taken into account, the swim-up technique seems to be sufficient for selecting spermatozoa in men with normal semen analyses. The nuclear maturity rate also correlates with sperm morphology and motility.

Influence of insulin resistance on total renin level in normotensive women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of insulin resistance on the plasma total renin level in normotensive women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Twenty-five normotensive women with PCOS were compared with 11 normotensive control women with regular cycles and no features of PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Insulin resistance was estimated by continuous infusion of glucose with model assessment in the early follicular phase. MAIN OUTCOME MEASURE(S): Plasma levels of total renin and angiotensin II and serum levels of gonadotropins, DHEAS, total T, free T, 17 alpha-hydroxyprogesterone, and PRL were determined. RESULT(S): Plasma concentrations of angiotensin II were similar in the PCOS group and the control group. The concentration of total renin in plasma was higher in women with PCOS than in healthy women independent of insulin resistance. The sensitivity and specificity of the plasma total renin level to diagnose women with PCOS were calculated as 80% and 71.4%, respectively. CONCLUSION(S): The plasma total renin level is higher in normotensive women with PCOS than in healthy women independent of insulin resistance.

Role of the mutations Trp8 => Arg and Ile15 => Thr of the human luteinizing hormone beta-subunit in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the clinical significance of LH in the form of a mutant beta-subunit in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Thirty healthy women and 30 women with PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the use of polymerase chain reaction and subsequent restriction fragment length polymorphism. MAIN OUTCOME MEASURE(S): Serum levels of gonadotropins, androgens, E2, and prolactin were determined, and the results of restriction fragment length polymorphism were analyzed. RESULT(S): Five women in the control group and one woman in the PCOS group were found to be affected by the LHbeta gene mutations. No difference was observed in serum androgen and E2 levels between the affected women and 25 healthy women who were homozygous for the wild-type LH. However, women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having mutant LH. CONCLUSION(S): The frequency of LH mutations in women with PCOS is similar to that in healthy women. The presence of the variant does not cause any significant change in serum levels of androgens and E2.

Ovarian stromal hypertrophy in polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between the ovarian stromal area and clinical hormonal characteristics in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Twenty-eight women with PCOS (group 1) and 26 healthy women (group 2) participated in this study. For measuring the ovarian stromal area, transvaginal ultrasonography was performed on all women during the early follicular phase of the menstrual cycle. Venous blood was sampled from the women to determine serum follicle stimulating hormone, luteinizing hormone (LH), estradiol, androstenedione, free testosterone (FT), total testosterone (TT), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate, and fasting insulin and glucose levels. Two-tailed t and Pearson correlation tests were used for statistical analysis. RESULTS: Women with PCOS were heavier, and their serum FT, TT and LH levels were significantly higher than in the normals (P < .001, P < .012 and P < .001, respectively). The ovarian stromal area measured by transvaginal ultrasonography was also significantly larger than in the normals (P < .001). Only basal serum insulin levels seemed to correlate positively with the ovarian stromal area in women with PCOS (r = .43 P = .09). CONCLUSION: Although transvaginal ultrasonography has played an important role in the evaluation of women with PCOS, we could not demonstrate a relationship between the ovarian stromal area and hormonal characteristics of PCOS. Therefore, transvaginal ultrasonography and hormonal parameters must be used as complementary diagnostic methods in women with PCOS.

Mammographic changes in women receiving tibolone therapy.

OBJECTIVE: To investigate the effects of tibolone therapy for menopausal symptoms on mammographic findings and to identify any association between mammographic changes and the demographic and hormonal characteristics of women receiving tibolone. DESIGN: A prospective study. SETTING: A university hospital. PATIENT(S): Seventy-five women who were in the climacteric or postmenopausal period were recruited, and 25 of them were followed up for 24 months. INTERVENTION(S): After high-resolution mammographies were performed and blood samples were collected, tibolone (2.5 mg/d) was administered orally to all patients. At the end of the 24-month follow-up period, blood samples were collected again and mammographies were repeated. MAIN OUTCOME MEASURE(S): Serum levels of LH, FSH, prolactin, estradiol, testosterone, and DHEAS were determined from the collected samples, and mammographies were interpreted. RESULT(S): At the end of the 24-month follow-up period, mammographic changes were observed in only two women (8%). Women who had no change in mammography constituted group I (n = 23). Women who had a change constituted group II (n = 2). Although the initial hormone levels were not different, the increase in serum DHEAS in group I was significantly higher than in group II (z = 2.30, P = 0.021). CONCLUSION(S): The frequency of mammographic changes in women receiving tibolone therapy was found to be 8% at the end of the 24-month follow-up. The serum DHEAS level may be an important hormonal marker complementary to mammographic screening for women receiving tibolone therapy. We strongly believe that tibolone is safe in terms of mammographic changes in postmenopausal women.