O. Gregoriou

Prevention and management of ovarian hyperstimulation syndrome.

Abstract:  The Ovarian Hyperstimulation Syndrome (OHSS) represents one of the biggest nightmares of all physicians involved in Assisted Reproductive Technologies (ART). Every year, several hundreds of women are hospitalized and to date several deaths have been reported. The pivotal event in the development of OHSS is the disruption of capillary integrity that results in leakage of intravascular fluid and proteins into third space. On the molecular level, human chorionic godadotropin (HCG) either exogenous or endogenous, functions as the triggering point for the production of vascular endothelial growth factor (VEGF) that is the main mediator to increase permeability on the vascular bed. Spontaneous OHSS has also been reported, either due to inappropriate activation of a mutant FSH receptor or due to very high levels of HCG during pregnancy. The available evidence on the several preventive and therapeutic approaches with special attention to level 1 evidence when available is also presented. OHSS is a self‐resolving condition and the main role of the physician is to correct and maintain the intravascular volume, to support renal function and respiration and prevent thrombotic events. An algorithm on the management of OHSS on an outpatient basis and in the hospital is based on the previous mentioned principles.

Clinical parameters linked with malignancy in endometrial polyps

Aim To investigate the association of different clinical parameters with the histological diagnosis and the prevalence of premalignant and malignant endometrial polyps. Method The study included 516 cases from January 2002 to December 2006. Possible risk factors such as age, menopause status, abnormal bleeding, obesity, hypertension, diabetes mellitus, hormone therapy, use of tamoxifen and size of polyp were investigated in relation to their association with the malignant potential of endometrial polyps. Results All cases of endometrial polyps underwent hysteroscopic resection; 96.9% of the cases were benign, 1.2% premalignant and 1.9% malignant. Premalignant and malignant endometrial polyps were significantly associated with advanced age (>60 years), menopause, obesity and diabetes. The malignant polyps were analyzed to eight endometrioid, one serous and one clear cell carcinoma. Conclusion The prevalence of premalignant and malignant endometrial polyps is very low. Advanced age, menopause, obesity and diabetes increase the risk of endometrial polyp malignancy.

Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios

OBJECTIVE To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E(2) ratios. DESIGN Prospective, nonrandomized study. SETTING Reproductive medicine clinic. PATIENT(S) The study group consisted of 29 infertile men with a low serum T/E(2) ratio (<10). INTERVENTION(S) Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months. MAIN OUTCOME MEASURE(S) Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E(2). In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated. RESULT(S) The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E(2) ratios improved both hormonal and semen parameters. CONCLUSION(S) This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy.

Effect of tibolone on postmenopausal women with myomas

OBJECTIVE The aim of this study is to assess the effect of Tibolone (Livial) on uterine fibroids in postmenopausal women. METHODS This study included 40 naturally postmenopausal women with at least one uterine fibroid measuring > 20 mm. All of theme were scanned by transvaginal ultrasonography. Patients were randomized into two groups. Group A (n = 20) were treated with Tibolone 2.5 mg daily for 1 year and group B (n = 20) did not received therapy. The size of the uterine fibroids was reevaluated on the end of the treatment. RESULTS No statistically significant difference was found in the mean volume of fibroids before and after treatment with Tibolone. The administration of Tibolone resulted in an increase of fibroid volume in three patients, whereas it remained constant in the majority of the patients (70%) and decreased in three patients. CONCLUSIONS Our results suggest that treating menopausal symptoms with Tibolone does not affect preexisting asymptomatic uterine fibroids.

Controlled ovarian hyperstimulation with or without intrauterine insemination for the treatment of unexplained infertility

Objective: To evaluate whether there are any benefits from intrauterine insemination (IUI) as opposed to timed intercourse (TI) in stimulated ovarian cycles in couples with longstanding, unexplained infertility. Methods: Forty‐six couples with diagnoses of unexplained infertility were evaluated in a crossover study after a total of 141 cycles. Sixty‐seven cycles were with IUI after controlled ovarian hyperstimulation (COH) while 74 cycles were after COH and TI. Results: The pregnancy rate after COH/TI was 16.7% and after COH/IUI 45.2%. Cycle fecundity however was 8.9% after COH/TI and 25.7% after COH/IUI, which is a statistically significant difference (P < 0.05). Conclusions: A trial of human menopausal gonadotropin and IUI is justified in couples with prolonged infertility of unknown cause.

Culture of seminal fluid in infertile men and relationship to semen evaluation.

Bacterial flora of the seminal fluid and its influence on semen quality, was examined in 225 asymptomatic unselected men. Each semen sample was cultured aerobically, anaerobically, for genital mycoplasmas, and for Chlamydia trachomatis. Semen analysis was made according to standard methods recommended by the W.H.O. All 225 semen samples had microbial isolates. All isolates had colony counts of 102 colony forming units (cfu/ml). Thirty‐three cases had > 102 cfu/ml, 85 cases had > 103 cfu/ml and 78 cases > 105 cfu/ml. The most common organisms isolated were Ureaplasma urealyticum in 86 samples and C. trachomatis in 26 samples. The most frequent abnormal parameters were viability (117 of 212, 52%), motility (85 of 212, 40%) and number of sperm cells (74 of 225, 32.8%). No significant correlation was found between abnormal semen parameters and presence of U. urealyticum, and C. trachomatis. We concluded that asymptomatic bacteriospermia (infection) in the semen did not significantly affect the count, motility or morphologic features of the specimen.

Fallopian tube sperm perfusion has no advantage over intra-uterine insemination when used in combination with ovarian stimulation for the treatment of unexplained infertility.

In this prospective randomized study we treated 60 couples with unexplained infertility with a combination of ovarian stimulation and either intrauterine insemination (IUI) or fallopian sperm perfusion (FSP). In the IUI we used a volume of 0.5 ml of inseminate and in the FSP a volume of 4 ml. The demographic characteristics of the patients, the stimulation parameters and the sperm data were not statistically different between the two groups. The pregnancy rate per cycle was 16.2% in the IUI group and 14.5% in the FSP group and the pregnancy rate per woman was 40 and 36.7%, respectively (not statistically different). We conclude that IUI and FSP are equally effective in the treatment of couples with unexplained infertility.

Pregnancy rates in gonadotrophin stimulated cycles with timed intercourse or intrauterine insemination for the treatment of male subfertility

OBJECTIVE To compare the pregnancy rates achieved by intrauterine insemination or timed intercourse in gonadotrophin stimulated cycles in couples whose only detectable abnormality was poor sperm quality. DESIGN Sixty-two couples with primary or secondary infertility due to male factor entered the study. The 62 couples were randomly equally divided into two groups. Each group began one of the two treatment modalities (controlled ovarian hyperstimulation in conjunction with timed intercourse or intrauterine insemination) for three consecutive cycles and then switched to the alternative treatment after one rest cycle, if pregnancy was not achieved. RESULTS Five pregnancies (3.9%) were achieved after 128 cycles with timed intercourse and 15 pregnancies (11.5%) after 130 cycles with intrauterine insemination. The difference was found to be statistically significant (P < 0.05). CONCLUSION We suggest that intrauterine insemination during hMG stimulated cycles improves the pregnancy rates of couples whose only detectable abnormality is poor sperm quality.

Effect of pentoxifylline on vascular endothelial growth factor C and flk-1 expression on endometrial implants in the rat endometriosis model

OBJECTIVE To investigate the effects of pentoxifylline, on vascular endothelial growth factor (VEGF)-C and flk-1 expression in the rat endometriosis model. DESIGN Prospective, randomized, placebo-controlled study. SETTING Academic institution. ANIMAL(S) Twenty Wistar rats with surgically induced endometriosis. INTERVENTION(S) Animals were evaluated after surgical induction of endometriosis and random allocation to a group that received pentoxifylline and a control group that received NaCl 0.9%, for 3 weeks. At the end of the treatment period the animals were killed and the implants evaluated macroscopically as well as by immunohistochemistry. MAIN OUTCOME MEASURE(S) Morphologic changes of the endometriotic implants; and evaluation of VEGF-C and flk-1 expression by a semiquantitative analysis (HSCORE) for the intensity of immunohistochemical reactivity. RESULT(S) A significant reduction was observed in the mean volume of the endometriotic implants per animal in the treatment group as compared with the control group. There was a significant reduction not only in the mean volume of implants per animal but also in the mean number of implants per animal after treatment. By immunohistochemical evaluation (HSCORE), there was a significant reduction in VEGF-C expression after treatment in all areas examined. A significant reduction of flk-1 expression was also noted in the glandular compartment after treatment but not in the epithelial surface or stroma. CONCLUSION(S) Pentoxifylline may cause suppression of endometriotic lesions by suppressing angiogenesis through VEGF-C and flk-1 expression.

The role of chlamydial serology in fertile and subfertile men

The incidence of serum antibodies to Chlamydia trachomatis and the possible association of a positive serology on semen parameters in 120 subfertile men were studied. The findings were compared with those of 120 fertile volunteers fathering two or more children. The two groups were divided into those without and those with a history of genito-urinary infection. There was no significant difference (p greater than 0.1) in the prevalence of antibody testing between the subgroups of fertile population. A statistically significant difference in the incidence of antibodies was found between the two subgroups of subfertile population. No significant difference was noted in the semen parameters between Chlamydia-positive and Chlamydia-negative fertile and subfertile patients.