Does progesterone supplementation improve pregnancy rates in clomiphene citrate and intrauterine insemination treatment cycles?

AIM: To investigate the effect of empiric use of luteal phase progesterone supplementation to improve endometrial receptivity in women undergoing treatment with clomiphene citrate in combination with intrauterine insemination (CC-IUI). DESIGN: Retrospective cohort analysis. SETTING: University fertility center. PATIENTS: 426 CC-IUI cycles from 292 patients with unexplained infertility. INTERVENTIONS: Patients were treated with micronized intravaginal progesterone 100 mg twice daily beginning approximately three days after CC-IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy per initiated cycle as defined by presence of fetal heart rate on ultrasound. RESULTS: Clinical pregnancy rate was higher in patients receiving luteal phase support compared to patients not receiving luteal phase support (odds ratio: 2.04; 95% confidence interval: 1.01-4.14) after adjusting for all factors in the analysis using a multivariate logistic regression model. Age at the start of the cycle, BMI and CC dose were not shown to have an effect on clinical pregnancy rates. Patients with endometrial lining (EML) thickness 6-8 mm and >8 mm had increased clinical pregnancy rates compared to EML <6 mm independent of luteal phase progesterone use. Patients who appear to receive the greatest benefit of progesterone supplementation are in the 6-8 mm EML cohort. CONCLUSIONS: Luteal phase progesterone supplementation in CC-IUI cycles can improve endometrial receptivity as judged by the improved clinical pregnancy rates as the primary outcome.

Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome.

The object of this retrospective cohort study was to determine if hCG levels correlate with ovarian hyperstimulation syndrome (OHSS) risk after adjustment for other risk factors during in vitro fertilization (IVF). We measured serum hCG approximately 12 h after hCG trigger in women undergoing 406 cycles of controlled ovarian hyperstimulation for IVF between June 2006 and December 2009. Serum hCG levels were measured 12 h after trigger. Bivariate logistic regression was used to assess the association between patient and cycle characteristics and OHSS. In our series, mild to moderate OHSS occurred in 9% (38/406), and severe OHSS diagnosed in 1.5% (6/406) of IVF cycles. OHSS risk was increased in younger women (<30 years old: adjusted odds ratio: aOR 2.46, 95% confidence interval: CI 1.14-5.34), increased number of oocytes (11-20: aOR 6.79, 95% CI 1.97-23.40; >20: aOR 17.55, 95% CI 4.84-63.70), and increase E2 levels (≥3,000 pg/mL: aOR 2.59, 95% CI 1.33-5.05), but was unrelated to hCG level (100-200 IU/L: aOR 1.53, 95% CI 0.60-3.91; ≥200 IU/L: aOR 1.42 95% CI 0.48-4.20). These results indicate that OHSS risk during IVF is unrelated to serum hCG level measured approximately 12 h after trigger.

Proteoglycans of uterine fibroids and keloid scars: similarity in their proteoglycan composition.

Fibrosis is the formation of excess and abnormal fibrous connective tissue as a result of either a reparative or reactive process. A defining feature of connective tissue is its extracellular matrix, which provides structural support and also influences cellular activity. Two common human conditions that result from fibrosis are uterine fibroids (leiomyomas) and keloid scars. Because these conditions share a number of similarities and because their growth is due primarily to excessive extracellular matrix deposition, we compared the proteoglycans of uterine fibroids and keloid scars with corresponding normal tissues. Our analysis indicates that uterine fibroids and keloid scars contain higher amounts of glycosaminoglycans relative to normal myometrium and normal adult skin respectively. Proteoglycan composition is also different in the fibrotic tissues. Compared with unaffected tissues, uterine fibroids and keloid scars contain higher relative amounts of versican and lower relative amounts of decorin. There is also evidence for a higher level of versican catabolism in the fibrotic tissues compared with unaffected tissues. These qualitative and quantitative proteoglycan differences may play a role in the expansion of these fibroses and in their excessive matrix deposition and matrix disorganization, due to effects on cell proliferation, TGF (transforming growth factor)-ß signalling and/or collagen fibril formation.

Diagnosis and management of endometrial hyperplasia.

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.

Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone Control, and Implications for Pathophysiology.

Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression.

Laparo endoscopic single site balloon vaginoplasty (LESS-BV).

OBJECTIVE: To evaluate feasibility, advantages, and disadvantages of the laparo-endoscopic single site surgery (LESS) technique for balloon vaginoplasty (BV). STUDY DESIGN: Cohort study. SETTING: Tertiary care facility. RESULTS: LESS-BV was successfully performed in 6 patients with Mullerian aplasia and one with androgen insensitivity syndrome (AIS). Patients presented with failure of intravaginal intercourse and/or dyspareunia. The procedure was performed successfully in conjunction with gonadectomy for the AIS case. The total operative time was 50-75 minutes. No operative complications were reported. Postoperative pain scores ranged from 0 to 2 points at rest and from 20 to 60 points during dressing change, increasing distension, and traction. The depths of the constructed neovaginas measured up to 12.8 cm. Sexual intercourse was initiated on the day of catheter removal. Penetrations and satisfactions scores increased to up 90 points for both partners. CONCLUSIONS: LESS-BV is technically feasible. LESS-BV allows better, stronger midline and long traction pass along the anatomic longitudinal axis of the hypoplastic vagina. Surgical outcomes should be compared prospectively to conventional laparoscopic BV.

Robotic surgery in gynecologic oncology.

Robotic surgery for the management of gynecologic cancers allows for minimally invasive surgical removal of cancer-bearing organs and tissues using sophisticated surgeon-manipulated, robotic surgical instrumentation. Early on, gynecologic oncologists recognized that minimally invasive surgery was associated with less surgical morbidity and that it shortened postoperative recovery. Now, robotic surgery represents an effective alternative to conventional laparotomy. Since its widespread adoption, minimally invasive surgery has become an option not only for the morbidly obese but for women with gynecologic malignancy where conventional laparotomy has been associated with significant morbidity. As such, this paper considers indications for robotic surgery, reflects on outcomes from initial robotic surgical outcomes data, reviews cost efficacy and implications in surgical training, and discusses new roles for robotic surgery in gynecologic cancer management.