1. The use of metformin for women with PCOS undergoing IVF treatment.
   
2. The association between polycystic ovaries and endometrial cancer.
   

Gynaecologic Oncology

3. Persistent HPV infection after conization in patients with negative margins.
   

Obstetrics/Sexual Medicine

4. Effect of coitus on recurrent preterm birth.
   

1. The use of metformin for women with PCOS undergoing IVF treatment.

Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). It was wished to explore the effect of metformin in women with PCOS undergoing IVF. Therefore, a randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate. One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022). It is concluded that short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.

Reference

Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006 Jun;21(6):1416-25. Epub 2006 Feb 24. PMID: 16501038 [PubMed - in process]

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2. The association between polycystic ovaries and endometrial cancer.

Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk of endometrial cancer (EC), albeit of a more differentiated type with better prognosis than in normal women. This study was designed to test these assumptions, as evidence for them is lacking. The prevalence of polycystic ovaries (PCO), as a marker of PCOS, was investigated in ovarian sections from 128 women with EC and 83 with benign gynaecological conditions. The expression of the prognostic markers p53, Ki67, Bcl2 and cyclin D1 was also investigated by immunohistochemistry in endometrial tumours from 11 women with PCO and 16 with normal ovaries. Overall, PCO were similarly prevalent in women with EC (8.6%) and benign controls (8.4%); however, in women aged <50 years, PCO were more prevalent in women with EC (62.5 versus 27.3%, P = 0.033). Cyclin D1-expressing endometrial tumours tended to be more prevalent in women with PCO compared to normal ovaries (36.4 versus 6.25%, respectively, P = 0.071). Bcl2-, p53- and Ki67-expressing tumours were similarly prevalent. The association between PCOS and EC appears confined to premenopausal women. The tendency for cyclin D1-expressing endometrial tumours to be more prevalent in women with PCO challenges the assumption that EC prognosis is improved in women with PCOS.

Reference

Pillay OC, Te Fong LF, Crow JC, Benjamin E, Mould T, Atiomo W, Menon PA, Leonard AJ, Hardiman P. The association between polycystic ovaries and endometrial cancer. Hum Reprod. 2006 Apr;21(4):924-9. Epub 2005 Dec 16. PMID: 16361289 [PubMed - in process

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3. Persistent HPV infection after conization in patients with negative margins.

The purpose of the study was to investigate the rate of clearance of high-risk HPV after conization with negative margins and to identify the factors that may predict high-risk HPV clearance/persistence after conization with negative margins. A retrospective review was performed of 69 patients (mean age 39.5 years, range 25-60 years) with histologically verified CIN 2 or CIN 3 who underwent electroknife conization with negative margins between March 2002 and December 2003. High-risk HPV testing was performed on cervical cytology prior to and 6 months after conization. Hybrid Capture II testing was used to detect HPV DNA. High-risk HPVs were detected in the primary cervical lesions of 67 of 69 patients (97.1%) prior to conization. Follow-up at 6 months revealed that high-risk HPVs were eradicated by conization in 82.1%. Univariate analysis showed that persistent HPV infection after conization with negative margins was more likely to occur when the pretreatment viral load was high (RLU/PC > 500) (P = 0.005). HPV infection after conization with negative margins was persistent in 43.8% (7/16) of patients with high viral load (RLU/PC > 500) and in 9.8% (5/51) of patients with low viral load (RLU/PC < or = 500). Multiple regression analysis showed that high viral load (RLU/PC > 500) was the only significant independent predictor of HPV persistence (P = 0.0027). High-risk HPV infections were effectively eliminated by conization with negative margins in most cases. Because high viral loads are significantly associated with high-risk HPV persistence after conization with negative margins, patients with high viral loads prior to conization should be closely followed.

Reference

Song SH, Lee JK, Oh MJ, Hur JY, Na JY, Park YK, Saw HS. Persistent HPV infection after conization in patients with negative margins. Gynecol Oncol. 2006 Jun;101(3):418-22. Epub 2006 Jan 4. PMID: 16386782 [PubMed - indexed for MEDLINE]

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4. Effect of coitus on recurrent preterm birth

The study was performed to estimate the impact of sexual behavior on the risk of recurrent spontaneous preterm birth at less than 37 weeks of gestation. This is a secondary analysis of a multicenter, blinded observational study of endovaginal sonographic examinations performed at 16-18 weeks of gestation on 187 women with singleton gestations who were at high risk for recurrent spontaneous preterm birth (prior spontaneous preterm birth at < 32 weeks of gestation). At the time of enrollment, each woman was interviewed by a research nurse with regard to her sexual history. The patient was asked about the number of sexual partners in her lifetime, the number of sexual partners since the start of her pregnancy, and, on average, the frequency of intercourse per week in the preceding month. A total of 165 pregnancies were available for this analysis. The population incidence of spontaneous preterm birth at less than 37 weeks of gestation in the study pregnancy was 36%. An increasing number of sexual partners in a woman's lifetime was associated with an increased risk of spontaneous preterm delivery (one partner 19%, 2-3 partners 29%, >or= 4 partners 44%, P = .007), whereas the number of sexual partners since the start of pregnancy was not (P = .42). Women who reported infrequent sexual intercourse during early pregnancy had an incidence of recurrent spontaneous preterm birth of 28% compared with 38% in those women who reported some intercourse (P = .35). Self-reported coitus during early pregnancy was not associated with an increased risk of recurrent preterm delivery. There was an association between increasing number of sexual partners in a woman's lifetime and recurrent preterm delivery. LEVEL OF EVIDENCE: II-2.

Reference

Yost NP, Owen J, Berghella V, Thom E, Swain M, Dildy GA 3rd, Miodovnik M, Langer O, Sibai B; National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network. Effect of coitus on recurrent preterm birth. Obstet Gynecol. 2006 Apr;107(4):793-7.

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