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The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.

Uterine myomas are the most common solid pelvic tumors in women and the primary indication for hysterectomy. Most of the myomas are asymptomatic. The most common symptoms associated with uterine myomas are abnormal uterine bleeding and pelvic discomfort mostly caused by the mass effect. Vaginal bleeding may lead to iron deficiency anemia. Uterine myomas have a significant role in reproductive dysfunction, although a causal relationship between infertility and intramural or subserosal myomas not disturbing the uterine cavity has not been established clearly. Nevertheless myomas, especially the tumors distorting the uterine cavity, are associated with infertility and spontaneous miscarriage. In addition, the myomas may be the potential cause for numerous obstetric complications, especially if they are located adjacent to placenta. The transformation of myomas to leiomyosarcomas is a very rare event. Leiomyosarcomas may be suspected in postmenopausal women with rapidly growing symptomatic solid pelvic mass. Despite the high prevalence of these tumors, there is paucity of data available regarding the natural clinical history of myomas.

Background: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation., Methods: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry., Results: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells., Conclusions: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.

Although the diagnosis of luteal phase defect (LPD) has been described convincingly in the research setting, it remains a controversial clinical entity. Apart from many uncertainties that surround the diagnosis of LPD, there is no convincing evidence that LPD is associated with infertility and recurrent abortion. Once diagnosed, the treatment options are empiric and include those that are recommended for unexplained infertility. The efforts to diagnose LPD in patients who have infertility or recurrent abortion are not justified.

Purpose of Review: Various methods have been proposed and are currently used in the assessment of ovarian reserve in order to predict the outcome in assisted reproduction. This review focuses on the current information regarding the ovarian reserve markers and tests, an active area of research., Recent Findings: Female age alone is a rough parameter for assessing ovarian reserve. The basal follicle stimulating hormone level is not adequately sensitive to predict poor outcome and the same is true for other basal parameters, including basal estradiol, the follicle stimulating hormone/luteinizing hormone ratio, and inhibin-B levels. The clomiphene citrate challenge test has a low sensitivity but this sensitivity is greater than that of basal follicle stimulating hormone. The value of other hormonal dynamic tests remains to be determined. Among the ultrasound markers the total antral follicle count seems to be promising. Ovarian biopsy in this assessment is controversial. History of poor response to ovarian stimulation is a strong indicator for declining ovarian function., Summary: There is currently no clinically useful predictive test sufficiently accurate and distinct in time from controlled ovarian stimulation to assess ovarian reserve accurately. Further research is warranted to validate the ovarian reserve tests in the general population and in populations with different causes of infertility.

In order to investigate the effect of hormone replacement therapy (HRT) on plasma homocysteine and C-reactive protein (CRP) levels 46 healthy postmenopausal women were prospectively enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone were administered. After 6 months, estrogen alone significantly increased serum CRP concentrations (p = 0.039), however, estrogen plus progesterone therapy did not significantly alter serum CRP levels. Both regimens significantly decreased plasma homocysteine levels (CEE group p = 0.034, CEE+MPA group p = 0.007). It was concluded that the reduction in plasma homocysteine levels with both regimens might contribute to the cardiovascular benefit of HRT and the CRP raising effect of estrogen might be partially prevented by the addition of progesterone., (Copyright 2002 S. Karger AG, Basel)

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.

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.

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.

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.

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.

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.

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.

Objective: To examine whether insulinlike growth factor I (IGF I), IGF II and IGF binding protein 3 (IGFBP 3) in serum and peritoneal fluid (PF) correlate with the presence and severity of endometriosis., Study Design: Case-control study including 29 patients with endometriosis and 15 controls. The revised American Fertility Society classification stages of I and II were pooled as early-stage (n = 15), and stages III and IV were taken as late stage (n = 14). Simultaneous sampling of blood and PF was performed during laparoscopy, and IGF I, IGF II and IGFBP 3 levels were determined by immunoradiometric assay., Results: The serum levels of all three proteins were higher than PF levels except for a reversed IGF I PF: serum ratio in the early stage. There were no significant differences in IGF II and IGFBP 3 levels among the groups. The mean serum IGF I levels of controls and early-stage patients were significantly lower than those in the late stage. Also, mean PF IGF I levels in controls were significantly lower than in the late stage., Conclusion: IGF I may be an important mediator in the development and/or maintenance of endometriosis or progression to late-stage disease.

Therapeutic manipulation of cytokines may be accomplished by inhibition of a particular cytokine using an antagonist or by administering the cytokine itself. Cytokines appear to have a number of physiological roles, and consequently therapeutic implications, in obstetrics and gynaecology. In the central nervous system, interleukin-1 (IL-1) decreases gonadotropin releasing hormone and luteinising hormone levels and increases prolactin levels. Interferon-alpha and -gamma and tumour necrosis factor-alpha have negative effects on sperm motility and penetration rates. Seminal IL-6 and IL-8 levels correlate negatively with fertility. IL-8 seems to be involved in periovulatory events by attracting and activating neutrophils that play a role in timely follicular rupture. Leukaemia inhibitory factor has been shown to be essential for blastocyst implantation. Interleukin-1 may be one of the signals for the onset of human parturition, and may also play a role in the initiation of preterm labour associated with intra-amniotic infection. In a mouse model, pretreatment with subcutaneous IL-1 receptor antagonist (IL-1ra) prevented IL-1-induced preterm parturition, suggesting a role for the use of anticytokine agents in the treatment of infection-associated preterm labour. IL-8 induces cervical ripening when applied locally to the cervix in rabbits, which indicates its pivotal role in cervical maturation. The evaluation of cytokine levels, especially IL-1, may be used as a diagnostic tool to monitor osteoporosis, and drugs such as IL-1ra that interfere with cytokine action could provide new therapies for the effective management of postmenopausal osteoporosis. In spite of all these possibilities, current cytokine-based therapies are still experimental, and numerous problems need to be resolved before they are used in routine clinical applications.

Objective: To investigate the effect of endometriosis on implantation., Design: Case-control study from Yale University IVF-ET program., Patients: Two hundred eighty-four consecutive IVF cycles were analyzed retrospectively. Patients with endometriosis only (n = 35; 89 cycles) were compared with an age-matched control group with tubal infertility (n = 70; 147 cycles) and also to a group with unexplained infertility (n = 15; 48 cycles). Data from the endometriosis group was analyzed further in subgroups of minimal-mild (43 cycles) and moderate-severe (46 cycles)., Results: No difference was found in the number and the quality of oocytes retrieved and fertilization rates between the endometriosis, the tubal infertility, and the unexplained infertility groups. The quality and the number of embryos transferred in each group were comparable. A trend toward reduced pregnancy rate per transfer (14.8%) in the endometriosis versus tubal or unexplained infertility groups (25.7% and 23.3%, respectively) was observed. Implantation rate (gestational sac per transferred embryo) was significantly lower in the endometriosis versus the tubal infertility group (3.9% versus 8.1%; unexplained infertility group, 7.2%). Analysis of first cycles only across all groups revealed that the implantation rate also was significantly lower in the endometriosis versus the tubal infertility group (3.1% versus 9%; unexplained infertility group, 6.7%). Within the endometriosis group, although the pregnancy rate per cycle and per transfer were similar in subgroups, patients with minimal-mild endometriosis had the lowest implantation rate., Conclusion: We conclude that, in patients with endometriosis, implantation rate is low. Abnormal implantation, which may be secondary to endometrial dysfunction or embryotoxic environment, is a factor in endometriosis-associated subfertility.