Endometriosis and the role of reproductive medicine.

Endometriosis is a complex trait with significant environmental and genetic influences that are likely to affect its phenotype. Natural history of the disease varies from one individual to another. The gold standard of surgical diagnosis is limited in accuracy by visibility and recognition of lesions by the attending surgeon. Several lines of evidence suggest that pelvic endometriosis results from the reflux of viable endometrial tissue through the fallopian tubes. Endometriosis is an inflammatory disease that nuclear factor kappa B pathway may play an important role in its pathogenesis. Endometriotic lesions demonstrate increased aromatase expression in association with increased cyclo-oxygenase-2 expression, especially in red lesions which represent earlier stages of inflammation. Estrogen and progesterone receptor expressions vary according to the morphology and the inflammatory status of the endometriotic lesions. Normal endometrial tissue fragments can adhere and implant to peritoneum. Aromatase expression, a possible intrinsic survival factor for endometrial tissue, is inducible in human endometrial fragments by androstenedione at physiological concentrations found in peritoneal fluid. Inflammatory response to ectopic endometrial tissue, which may vary in each individual seems to be important in disease progression. Current therapies for endometriosis include surgical and medical approaches aimed at cytoreduction or hormonal suppression. However, the disease have tendency to recur in many symptomatic women. Although new management approaches are emerging, properly designed clinical trials are desperately needed in treatment of pain and subfertility associated with endometriosis. Future studies should also focus on identifying risk population to develop preventive strategies, since the treatment of endometriosis is costly and challenging.

The effect of intramural and subserous uterine fibroids on implantation and clinical pregnancy rates in patients having intracytoplasmic sperm injection.

Our objective was to assess the effects of intramural and subserous fibroids on intracytoplasmic sperm injection (ICSI) in a retrospective case-control study of 108 women with uterine fibroids and 324 controls. The fibroids were located and measured by transvaginal ultrasound performed just before the ICSI cycle and all patients had normal endometrial scan. Seventy-three women had intramural and 35 women had subserous fibroids and the maximum diameter in any patient ranged from 0.5-10 cm. The number of fibroids in a patient ranged from 1-8. The first cycle outcome was compared with an age and body mass index matched 324 ICSI patients/cycles. All couples had male factor infertility. The ICSI cycles of patients with intramural and subserous fibroids were comparable in terms of the days of ovarian stimulation, the total dose of gonadotropin used, estradiol level on day of hCG administration, the number of metaphase II oocytes retrieved, fertilization and cleavage rates, number and quality of embryos developed and transferred. The implantation and clinical pregnancy rates were similar. We conclude that the presence of intramural and subserous fibroids does not adversely effect clinical pregnancy and implantation rates in patients undergoing ICSI.

Hormone replacement therapy to improve left ventricular diastolic functions in healthy postmenopausal women.

OBJECTIVES: To investigate the effects of estrogen and estrogen plus progesterone replacement therapy on left ventricular systolic and diastolic function parameters in healthy postmenopausal women. METHODS: Forty-six healthy consecutive postmenopausal women were prospectively enrolled. Hormone replacement therapy (HRT), which was either 0.625 mg/day conjugated equine estrogen (CEE) alone, or with 2.5 mg/day medroxyprogesterone acetate (MPA) was administered depending on the hysterectomy status. Left ventricular systolic and diastolic function parameters were evaluated with echocardiography before and after 6 months of HRT. The paired t-test was used for statistical analysis. RESULTS: Estrogen or estrogen plus progesterone did not significantly alter the left ventricular dimensions and systolic function parameters. However, significant improvements were noted in several diastolic function parameters including late diastolic mitral flow velocity, ratio of early to late mitral flow velocity and isovolumic relaxation time (P=0.003, P=0.001 and P=0.005, respectively, for the CEE group; all P<0.001 for the CEE+MPA group). CONCLUSIONS: Estrogen or estrogen plus progesterone replacement therapy may significantly improve left ventricular diastolic functions in healthy postmenopausal women.

Effects of hormone replacement therapy on heart rate variability in postmenopausal women.

BACKGROUND: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6-month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. METHODS: Forty-six healthy postmenopausal women (age 48 +/- 5, range 40-60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. RESULTS: A 6-month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 +/- 11.8 ms before HRT significantly increased to 35.4 +/- 16.7 ms after 6 months (P = 0.011). CONCLUSION: Our results indicate that a 6-month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardioprotective effect(s) of HRT.

A prospective evaluation of the effect of salpingectomy on endometrial receptivity in cases of women with communicating hydrosalpinges.

BACKGROUND: We aimed to assess whether salpingectomy in women with communicating hydrosalpinges influenced endometrial receptivity. METHODS: The inclusion criteria were: women with communicating hydrosalpinges, absence of other confounding infertility factors and aged <40 years. Patients were scheduled for laparoscopy during the putative window of implantation (cycle days 19-21). In patients in whom salpingectomy was decided upon due to the severity of tubal disease (n = 10), an intra-operative endometrial biopsy was performed. Post-treatment endometrial sampling was done between day 19-21 of the fourth consecutive cycle. Pre-treatment and post-treatment samples were assessed by both conventional histologic criteria and alpha(v)beta3 integrin immunostaining, where histological score (HSCORE) was used for quantification. RESULTS: Despite normal histological maturation assessed by conventional criteria, 8/10 hydrosalpinx cases yielded an epithelial HSCORE of <0.7, which was below the accepted threshold. Following salpingectomy, luminal endometrial epithelium demonstrated a significantly increased alpha(v)beta3 integrin expression (Wilcoxon's signed rank test, P = 0.017). Although the mean HSCORE for glandular epithelia improved, it failed to reach statistical significance. Ultrasound visible hydrosalpinges (n = 5) and non-visible cases (n = 5) were also compared. However, neither the pre-treatment integrin expression, nor the postoperative improvement were significantly different between these groups. CONCLUSIONS: We conclude that the surgical treatment of communicating hydrosalpinges may improve endometrial receptivity as assessed by alpha(v)beta3 integrin expression. Women with hydrosalpinges may undergo endometrial evaluation by the molecular markers of implantation, such as alpha(v)beta3 integrin. This evaluation may be decisive in determining the optimal management of cases, and may also be used to assess the efficacy of the treatment. The expression of the implantation markers should be correlated with implantation and clinical pregnancy rates in IVF-embryo transfer programs.

Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome.

OBJECTIVE: To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). DESIGN: A prospective case-control study. SETTING: University-based hospital. PATIENT(S): Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls. INTERVENTION(S): Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12), folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured. MAIN OUTCOME MEASURE(S): Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels. RESULT(S): The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak (r = -0.474). The mean fasting insulin level correlated negatively with mean E/A ratio (r = -0.387). CONCLUSION(S): Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.

Hormone replacement therapy shortens QT dispersion in healthy postmenopausal women.

BACKGROUND: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. METHODS: Fifty-one consecutive healthy postmenopausal women (age 48 +/- 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12-lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. RESULTS: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 +/- 13 ms vs 38 +/- 13 ms, P = 0.01; for CEE + MPA group 49 +/- 14 ms vs 36 +/- 13, P < 0.001). CONCLUSION: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified.

The presence and extent of endometriosis do not effect clinical pregnancy and implantation rates in patients undergoing intracytoplasmic sperm injection.

OBJECTIVE: To assess the impact of endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN: Retrospective case-control study which enrolled 1280 consecutive cycles of 834 couples of ICSI with ejaculated sperm. Among them, 973 cycles of 632 couples had resulted in embryo transfer (ET). The presence of endometriosis was noted in 110 consecutive cycles of 45 patients among which 78 cycles of 44 patients had resulted in ET. Data from endometriosis group were analyzed in subgroups of minimal-mild (49 ET cycles of 25 patients) and moderate-severe (29 ET cycles of 19 patients). The controls consisted of 1170 consecutive cycles of age-matched 771 couples. Of the controls, 588 couples had 895 cycles of ET. Main outcome measures were implantation and clinical pregnancy rates. RESULTS: There were no differences in cycle and ET cancellation rates between control and endometriosis groups. The number of oocytes retrieved, fertilization and cleavage rates and the number and quality of embryos developed and transferred were similar among the groups. The implantation and clinical pregnancy rates were also comparable. CONCLUSION: The presence and extent of endometriosis do not affect implantation and clinical pregnancy rates in patients undergoing ICSI.

Short-term effects of three continuous hormone replacement therapy regimens on platelet tritiated imipramine binding and mood scores: a prospective randomized trial.

OBJECTIVE: To evaluate the effects of continuous hormone replacement therapy (HRT) regimens on platelet-tritiated ((3)H-) imipramine binding (Bmax) and mood. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S): Sixty postmenopausal patients. INTERVENTION(S): Randomization to 3 months of daily treatment with tibolone and conjugated equine estrogen (CEE).625 mg combined either with 2.5 or 5 mg of medroxyprogesterone acetate (MPA). The inclusion criteria-matched patients declined for HRT were prescribed daily alendronate. Pre- and posttreatment blood sampling for Bmax and mood evaluation with the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were done. MAIN OUTCOME MEASURE(S): Pre- and posttreatment Bmax and mood scores. RESULT(S): As compared with baseline, both CEE+MPA regimens and tibolone significantly increased Bmax. The comparisons of percent change from baseline Bmax for the CEE+MPA and tibolone groups were similar. All three HRT regimens improved the BDI significantly, while there were no significant changes in the STAI. In the alendronate group, there were no significant changes in both pre- and posttreatment Bmax and mood scores. CONCLUSION(S): Continuous treatment with CEE+MPA and tibolone increases platelet (3)H-imipramine binding and improves mood. Mood-enhancing effects of tibolone may occur through the serotonergic system, as is the case with estrogen.

The origin of spermatozoa does not affect intracytoplasmic sperm injection outcome.

OBJECTIVE: To assess whether the origin of spermatozoa, ejaculate or testicular, affects intracytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN: Retrospective study of 890 consecutive first ICSI and embryo transfer cycles done for male infertility. The ICSI outcome of ejaculated spermatozoa (n=780) and testicular spermatozoa retrieved from patients with obstructive azoospermia (n=43), non-obstructive azoospermia (n=53) and severe oligoasthenoteratozoospermia (n=14) were compared by using chi-square test, independent t-test and ANOVA with Bonferroni test. RESULTS: All azoospermic males had a diagnostic testicular biopsy at least 6 months before the ICSI procedure. Spermatozoa were successfully retrieved in all 43 patients with obstructive azoospermia and in 72.6% of 73 non-obstructive cases. The cycle characteristics of the four groups were similar apart from a younger mean female age in the non-obstructive azoospermia group when compared with the ejaculated spermatozoa group. The fertilization, implantation and clinical pregnancy rates were comparable among the four groups. CONCLUSION: Testicular spermatozoa recovered from patients with obstructive and all types of non-obstructive azoospermia were as much as effective as ejaculated spermatozoa in ICSI.

Combined bilateral ectopic and intrauterine pregnancy following ovulation induction with the low-dose step-up protocol in a patient with polycystic ovary syndrome.

A woman with polycystic ovary syndrome (PCOS) developed bilateral tubal and an intrauterine pregnancy following ovulation induction with urinary FSH using the low-dose step-up protocol. After a spontaneous miscarriage she was treated by laparoscopic left salpingectomy and right linear salpingotomy.

Laparoscopic high lateral transposition of both ovaries before pelvic irradiation.

Lateral ovarian transposition before pelvic irradiation may preserve ovarian function in young women with gynecologic or nongynecologic cancer. We performed high lateral, transposition of both ovaries in a 17-year-old woman with primary non-Hodgkin lymphoma of the sacrum with subsequent preservation of menstrual cyclicity.

Leukocytes in ovarian function.

It has become apparent that in the ovary, the immune system contributes to the regulation of gonadal function. Leukocytes present within the ovary may constitute potential in-situ modulators of ovarian function that act through local secretion of regulatory soluble factors. These factors include numerous cytokines that largely originate by the action of immune cells within the ovary. Actual rupture of the follicle during ovulation may be dependent on tissue remodelling that is characteristic of an acute inflammatory reaction and includes mobilization of thecal fibroblasts, increased leukocyte migration, release of various mediators and loosening of connective tissue elements in the follicle wall. Both corpus luteum formation and luteal regression also involve progressive infiltration of lymphocytes and macrophages, release of chemokines and cytokines, and communication through cell adhesion molecules. In this review, we examine the evidence for the leukocytes and their products in regulation of ovarian function and relate the potential significance of these cells and substances to some ovarian disorders.

Mature cystic teratomas of the ovary: case series from one institution over 34 years.

OBJECTIVE: To evaluate bilaterality, complications and malignant changes of mature cystic teratomas of the ovary. STUDY DESIGN: Retrospective study of 501 patients operated at Hacettepe University Hospital between the years of 1964 and 1998. RESULTS: The median age was 35 years (range 13-76). One hundred and six cases (21.1%) were asymptomatic. The mean tumor diameter was 7.0+/-4.5 cm. The decision for cystectomy or oophorectomy was related with the patient age, gravidity and parity. The bilaterality rate when both ovaries were evaluated histopathologically was 13.2% (44/331). Total complication rate was 10.7%, torsion being the most frequent (4.9%). The rate of malignant transformation was 1.4%. CONCLUSION: Ovarian mature cystic teratomas are common tumors especially during the reproductive period with low rates of covert bilaterality, complications and malignant transformation. The treatment should be directed on the basis of age, fertility desire or presence of another pelvic pathology rather than the size or bilaterality.

Perinatal outcome in adolescent pregnancies: a case-control study from a Turkish university hospital.

OBJECTIVE: To determine whether adolescent pregnancy is associated with increased risk for adverse pregnancy outcome. STUDY DESIGN: Retrospective case-control study which enrolled 1460 singleton adolescent pregnancies and 2980 controls, delivered at Hacettepe University Hospital between January 1990 and January 1998. RESULTS: Significantly higher rate of perinatal and severe perinatal complications were noted in adolescents. The presence of historical risks, multiparity, young age and lack of prenatal care were significant predictors of these complications. Exclusion of them except for age, revealed comparable perinatal and severe perinatal complications in both groups. CONCLUSION: Adolescent women who receive adequate prenatal care are at no greater risk of an adverse obstetric outcome than adult women of a similar sociodemographic background.

Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial.

OBJECTIVE: To compare the efficacy of intracytoplasmic sperm injection and IVF in women with a tuboperitoneal factor as their sole cause of infertility. DESIGN: Prospective, randomized study. SETTING: Hacettepe University Assisted Reproduction Unit, Ankara, Turkey. PATIENT(S): Seventy-six consecutively seen patients with tuboperitoneal factor infertility were randomized on an alternate basis to undergo either intracytoplasmic sperm injection (38 patients and cycles) or IVF (38 patients and cycles). INTERVENTION(S): Intracytoplasmic sperm injection and IVF. MAIN OUTCOME MEASURE(S): Fertilization, implantation, and clinical pregnancy rates. RESULT(S): A comparable number of oocytes and embryos were obtained with intracytoplasmic sperm injection and IVF. The two-pronuclei fertilization rates per metaphase II oocyte or mature cumulus-oocyte complex were similar in the two groups. The numbers of total and grade I embryos transferred also were similar. Comparisons of intracytoplasmic sperm injection and IVF did not reveal any statistically significant differences in individual implantation rates (38.75% +/- 24.46% and 34.58% +/- 16.97%, respectively) clinical pregnancy rates per cycle (21.05% and 21.05%, respectively), or take-home infant rates (18.42% and 15.79%, respectively). The type of procedure performed was not a significant predictor of clinical pregnancy. CONCLUSION(S): When a decision is made to proceed with an assisted reproductive technique in patients with a tubal factor as their sole cause of infertility, IVF should be the initial treatment of choice.

Increasing the daily dose of recombinant follicle stimulating hormone (Puregon) does not compensate for the age-related decline in retrievable oocytes after ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 6) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH, Puregon) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation. In all, 138 women were treated with recombinant FSH, 67 with 150 IU and 71 with 250 IU. The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group (not significant). In the 30-33 years of age class receiving the 250 IU dose, a surplus of 4.2 oocytes (14.8 versus 10.6) was found, whereas in the 37-39 age class nearly one oocyte more was retrieved in the 150 IU group (8.1 versus 7.4). The total dose used to reach the criterion for human chorionic gonadotrophin (HCG) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women (P < 0. 001). No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected, or the total dose. It is concluded that in women between 30 and 39 years of age, the decline in number of oocytes retrieved with increasing age cannot be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU.

Postpartum oral glucose tolerance tests in mothers of macarosomic infants: inadequacy of current antenatal test criteria in detecting prediabetic state.

OBJECTIVE: To assess the presence of subtle carbohydrate metabolism abnormalities in otherwise healthy mothers who have given macrosomic birth by utilizing postpartum oral glucose tolerance test (PPOGTT). STUDY DESIGN: Prospective controlled study enrolled gestational diabetic women (GDM, n=10), mothers with macrosomic infants (MwMIs, n=62) and controls (n=50). RESULTS: Receiver operating characteristic (ROC) curve analysis revealed that incremental 1-h+2-h PPOGTT value >111 mg/dl had a sensitivity of 80% and specificity of 78% in predicting antecedent diabetes. PPOGTT results were positive in 53.2% of MwMIs and 28% of controls (P<0.01). Maternal low-density lipoprotein and triglyceride levels, 50 gram glucose challenge test (50 g GCT) values and neonatal weight were the significant predictors of PPOGTT results. ROC analyses suggested that threshold of 50 g GCT should be lowered in order to better predict subjects with both macrosomia and positive PPOGTT. CONCLUSION: PPOGTT may identify a subset of women with macrosomic infants who have metabolic alterations of a prediabetic state. The discrepancies between antenatal and postpartum tests may reflect the need for redefinition of currently utilized criteria in screening and diagnosis of GDM.

Total corporal synechiae due to tuberculosis carry a very poor prognosis following hysteroscopic synechialysis.

Twelve consecutive patients with total corporal synechiae due to tuberculosis were reviewed in terms of intrauterine adhesion re-formation rate following hysteroscopic surgery. All patients presented with secondary amenorrhoea and infertility. The diagnosis was based on a 'glove finger appearance' at hysterosalpingography and classical laparoscopic and tubal biopsy findings. Intrauterine synechiae re-formation was assessed by postoperative hysterosalpingograms performed 3-4 months after the procedure. The 12 patients underwent 15 attempts for hysteroscopic lysis of total corporal synechiae. Three perforations occurred and all were managed with laparoscopic extracorporal suturing. Ultimately, adequate uterine cavity was obtained in all cases. Total intracorporal synechiae recurred in all patients at control postoperative hysterosalpingograms. We conclude that total corporal synechiae caused by tuberculosis, unlike other causes, carry a poor prognosis following hysteroscopic lysis. Surrogacy may be the only option for fertility in such couples.

Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate-resistant, normogonadotropic,chronic anovulation: a prospective randomized study.

OBJECTIVE: To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation. DESIGN: Prospective, randomized trial. SETTING: University-based infertility clinic. PATIENT(S): Fifty-one women. INTERVENTION(S): Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken. MAIN OUTCOME MEASURE(S): Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate. RESULT(S): Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered. CONCLUSION(S): Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.