George R. Attia

Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome

OBJECTIVE Metformin has been used as a treatment in many studies of the infertility associated with polycystic ovary syndrome (PCOS). We will review the literature on this topic as it specifically relates to changes in body mass index (BMI), improvement in menstrual cyclicity, and effects on ovulation and pregnancy rates. DESIGN Review of studies addressing biochemical and clinical changes in women with PCOS on metformin. MAIN OUTCOME MEASURE(S) Changes in BMI, menstrual cyclicity, ovulation rate, and pregnancy rate. RESULT(S) Metformin has been shown to produce small but significant reductions in BMI. Multiple observational studies have confirmed an improvement in menstrual cyclicity with metformin therapy. The studies addressing the concomitant use of metformin with clomiphene citrate initially predicted great success, but these have been followed by more modest results. There is little data in the literature concerning the use of metformin and hMGs. CONCLUSION(S) Some (but not all) women with PCOS have improvements in their menstrual cycles while on metformin. The data supporting the use of metformin in ovulation induction with clomiphene citrate and hMG remain to be confirmed by large, randomized, prospective studies.

Pregnancy outcomes by intravaginal and intrauterine insemination in 82 couples with male factor infertility due to spinal cord injuries

OBJECTIVE To report our centers pregnancy rates (PR) by intravaginal insemination (IVI) or intrauterine insemination (IUI) in 82 couples with male partners with spinal cord injuries. DESIGN Retrospective analysis. SETTING Major medical center. PATIENT(S) Male patients with spinal cord injuries and their female partners. INTERVENTION(S) Intravaginal insemination and IUI. MAIN OUTCOME MEASURE(S) Pregnancy and live birth outcomes. RESULT(S) Overall, 31 of the 82 couples (37.8% PR) achieved 39 pregnancies. Sperm were obtained by masturbation, penile vibratory stimulation, or electroejaculation in 4 men (4.9%), 42 men (51.2%), and 36 men (43.9%), respectively. Intravaginal insemination, performed mostly at home by selected couples, was undertaken in 45 couples, 17 of whom (37.8% PR) achieved 20 pregnancies. Intrauterine insemination was performed in 57 couples, 14 of whom (24.6% PR) achieved 19 pregnancies, with a cycle fecundity of 7.9%. Eighteen and 21 live births occurred by IVI and IUI, respectively. CONCLUSION(S) The methods of IVI and IUI are reasonable options for this patient population. These methods warrant consideration before proceeding to assisted reproductive technologies (ART).

Transforming growth factor β inhibits steroidogenic acute regulatory (StAR) protein expression in human ovarian thecal cells

In this study, we investigated the effects of TGFbeta1 on steroidogensis and expression of the steroidogenic acute regulatory (StAR) protein which regulates an important early step in the steroidogenic pathway. We utilized a human ovarian thecal like tumor (HOTT) cell model and investigated the effects of activin-A, inhibin-A, or TGFbeta1 in the presence of forskolin and the effect of dibutyryl cyclic AMP (dbcAMP) on steroid accumulation in the culture medium. Cells were also treated with different concentration of TGFbeta1 in the presence of forskolin, combined steroid production was measured at the end of 48 h and after 3 h incubation with 22R-hydroxycholesterol. In the presence of TGFbeta1 there was a dose-dependent inhibition of androstenedione production. Inhibition in combined steroid production was apparent at the highest concentration of TGFbeta1 tested. In the presence of 22R-hydroxycholesterol, combined steroid production was significantly inhibited at lower concentrations. TGFbeta1 inhibited StAR protein expression in a concentration dependent manner. There was also a similar inhibition in StAR mRNA. These results suggest that the effect of TGFbeta1 on steroid production and possibly follicular development may be in part due to its effects on StAR expression.

Virilization from partner's use of topical androgen in a reproductive-aged woman

A woman presented with virilization symptoms and elevated testosterone; however, a neoplastic source of excess androgen was not found on imaging. Eventually, the patient revealed she was exposed to transdermal testosterone used by her partner. This case highlights the importance of considering exogenous androgens in the differential diagnosis of virilization.

Anejaculatory infertility due to multiple sclerosis

There are few reports of pregnancy outcomes in couples with anejaculatory infertility secondary to multiple sclerosis and no longitudinal reports of semen quality in this population. We report our experience with one such case. The couple achieved two live births from spermatozoa obtained with electroejaculation: the first by intrauterine insemination and the second by in vitro fertilisation with intracytoplasmic sperm injection of donor oocytes. Linear regression analysis showed no progressive decline in semen parameters across 26 semen retrievals performed over 7.7 years. Years of disease do not appear to cause progressive decline in semen quality.