1. Second curettage in persistent trophoblastic disease.
   
2. Letrozole and tamoxifen in postmenopausal women with early breast cancer.
   

Obstetrics – Perinatal Medicine

3. Progesterone for prevention of recurrent preterm birth.
   

Reproductive Medicine

4. Low-dose aspirin and ovarian response and pregnancy rate.
   
5. Effect of endometriosis on IVF/ICSI outcome.
   

1. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey.

The objective of the study was to assess the curative effect of a second curettage in patients with low-risk Persistent Trophoblastic Disease (PTD) after molar pregnancy. A retrospective cohort survey was performed on 2122 patients registered with the Dutch Central Registry for Hydatidiform Moles between 1987 and 2003. Of these, 422 patients developed PTD. For various reasons, 128 patients were excluded. The study group comprised 85 patients with, according to the Dutch guidelines, low-risk PTD who underwent a second therapeutic curettage as a part of the treatment for PTD. The control group consisted of 209 patients with low-risk PTD who did not undergo a second curettage. Patients in the study and control group were classified for high/low-risk PTD according to the internationally accepted FIGO 2000 guidelines. Primary outcome measures were the need for chemotherapy and if applicable, the number of chemotherapy courses. After second curettage, eight out of 85 patients (9.4%) did not need additional chemotherapy which significantly differs from the 209 patients in the control group who all needed chemotherapy (P < 0.001). A debulking effect of the second curettage was observed: a median of 6 courses (interquartile range 3 courses) in the control group versus 5 courses (interquartile range 3 courses) in the study group (P = 0.036). Four out of the 85 (4.8%) patients with a second curettage had a major complication (uterine perforation or hemorrhage), which was managed conservatively. A second curettage cured 9.4% of patients with PTD in this historical cohort and reduces the number of courses of chemotherapy. A second curettage seems to benefit only a limited number of patients with PTD. A randomized controlled prospective trial is needed to confirm this observation.

Reference

van Trommel NE, Massuger LF, Verheijen RH, Sweep FC, Thomas CM. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol. 2005 Oct;99(1):6-13.

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2. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.

The aromatase inhibitor letrozole is a more effective treatment for metastatic breast cancer and more effective in the neoadjuvant setting than tamoxifen. Letrozole was compared with tamoxifen as adjuvant treatment for steroid-hormone-receptor-positive breast cancer in postmenopausal women. The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial that compared five years of treatment with various adjuvant endocrine therapy regimens in postmenopausal women with hormone-receptor-positive breast cancer: letrozole, letrozole followed by tamoxifen, tamoxifen, and tamoxifen followed by letrozole. This analysis compares the two groups assigned to receive letrozole initially with the two groups assigned to receive tamoxifen initially; events and follow-up in the sequential-treatment groups were included up to the time that treatments were switched. A total of 8010 women with data that could be assessed were enrolled, 4003 in the letrozole group and 4007 in the tamoxifen group. After a median follow-up of 25.8 months, 351 events had occurred in the letrozole group and 428 events in the tamoxifen group, with five-year disease-free survival estimates of 84.0 percent and 81.4 percent, respectively. As compared with tamoxifen, letrozole significantly reduced the risk of an event ending a period of disease-free survival (hazard ratio, 0.81; 95 percent confidence interval, 0.70 to 0.93; P=0.003), especially the risk of distant recurrence (hazard ratio, 0.73; 95 percent confidence interval, 0.60 to 0.88; P=0.001). Thromboembolism, endometrial cancer, and vaginal bleeding were more common in the tamoxifen group. Women given letrozole had a higher incidence of skeletal and cardiac events and of hypercholesterolemia. It is concluded that in postmenopausal women with endocrine-responsive breast cancer, adjuvant treatment with letrozole, as compared with tamoxifen, reduced the risk of recurrent disease, especially at distant sites. (ClinicalTrials.gov number, NCT00004205.) Copyright 2005 Massachusetts Medical Society.

Reference

Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardly A, Price KN, Goldhirsch A; Breast International Group (BIG) 1-98 Collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57.

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3. Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery.

Preterm birth occurs in 1 of 8 pregnancies and may result in significant morbidity and mortality. 17-alpha hydroxyprogesterone caproate (17-OHP caproate) has been found to be efficacious in reducing the risk of subsequent preterm delivery in women who have had a previous spontaneous preterm birth (sPTB). This analysis was undertaken to evaluate if 17-OHP caproate therapy works preferentially depending on the gestational age at previous spontaneous delivery. We hypothesized that treatment with 17-OHP caproate is more effective in prolonging pregnancy depending on the gestational age of the earliest previous preterm birth (20-27.9, 28-33.9 vs 34-36.9 weeks). This study was a secondary analysis of 459 women with a previous sPTB enrolled in a randomized controlled trial evaluating 17-OHP caproate versus placebo. Effectiveness of 17-OHP caproate for pregnancy prolongation was evaluated based on gestational age at earliest previous delivery according to clinically relevant groupings (20-27.9, 28-33.9, and 34-36.9 weeks). Statistical analysis included the chi-square, Fisher exact, and Kruskal-Wallis tests, logistic regression, and survival analysis using proportional hazards. Gestational age at earliest previous delivery was similar between women treated with 17-OHP caproate or placebo (P = .1). Women with earliest delivery at 20 to 27.9 weeks and at 28 to 33.9 weeks delivered at significantly more advanced gestational age if treated with 17-OHP caproate than with placebo (median 37.3 vs 35.4 weeks, P = .046 and 38.0 vs 36.7 weeks, P = .004, respectively) and were less likely to deliver <37 weeks (42% vs 63%, P = .026 and 34% vs 56%, P = .005, respectively). Those with earliest delivery at 34 to 36.9 weeks were not significantly different between 17-OHP caproate or control. It is concluded that 17-OHP caproate therapy given to prevent recurrent PTB is associated with a prolongation of pregnancy overall, and especially for women with a previous spontaneous PTB at <34 weeks.

Reference

Spong CY, Meis PJ, Thom EA, Sibai B, Dombrowski MP, Moawad AH, Hauth JC, Iams JD, Varner MW, Caritis SN, O'Sullivan MJ, Miodovnik M, Leveno KJ, Conway D, Wapner RJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1127-31.

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4. Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study.

Poor ovarian and endometrial responses to gonadotrophin stimulation in assisted reproduction techniques lead to decreased pregnancy rates. The aim of the present study was to test the hypothesis that low-dose aspirin started prior to controlled ovarian stimulation improves ovarian responsiveness, pregnancy rate (PR) and pregnancy outcome. A total of 374 women who were to undergo IVF/ICSI were randomized to receive 100 mg of aspirin (n=186) or placebo (n=188) daily. Treatment was started on the first day of controlled ovarian stimulation. It was continued until menstruation or a negative pregnancy test. Pregnant women continued the medication until delivery. The main outcome measures were the number of oocytes, number and quality of embryos, the clinical PR and pregnancy outcome. The mean (+/-SD) number of oocytes (12.0+/-7.0 versus 12.7+/-7.2), the total mean number of embryos (5.82+/-4.35 versus 5.99+/-4.66), the mean number of top quality embryos (0.99+/-1.39 versus 1.18+/-1.51) and the number of embryos transferred (1.64+/-0.64 versus 1.63+/-0.71) did not differ in the aspirin and placebo groups. Between the aspirin and placebo group, there was no statistically significant difference in clinical PR per embryo transfer (25.3%, n=44 out of 174 versus 27.4%, n=48 out of 175) or clinical PR per cycle initiated (23.7% versus 25.5%). Birth rate per embryo transfer did not differ significantly between the aspirin (18.4%) and placebo (21.1%) groups. The incidence of poor responders [12 (6.5%) versus 13 (6.9%)] was similar in both groups. The present results indicate that low-dose aspirin treatment does not have any beneficial effect on ovarian responsiveness, PR and pregnancy outcome in unselected women undergoing IVF/ICSI.

Reference

Pakkila M, Rasanen J, Heinonen S, Tinkanen H, Tuomivaara L, Makikallio K, Hippelainen M, Tapanainen JS, Martikainen H. Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study. Hum Reprod. 2005 Aug;20(8):2211-4. Epub 2005 Apr 7

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5. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates.

Women with endometriosis often need IVF to conceive-most women need several cycles of treatment. To evaluate the impact of moderate to severe endometriosis on cumulative IVF outcome, an observational study was carried out on 98 consecutive women who underwent IVF or ICSI treatment and had endometriosis diagnosed by laparoscopy or laparotomy and classified as minimal to mild endometriosis (American Society for Reproductive Medicine I/II) (n = 31) or moderate to severe endometriosis (American Society for Reproductive Medicine III/IV) (n = 67). The reference group consisted of 87 consecutive women with tubal infertility. The main outcome measures were cumulative pregnancy and live birth rates. There was a significantly lower pregnancy rate per fresh embryo transfer after pooled cycles (1-4) among women with stage III/IV endometriosis (22.6%) compared to stage I/II group (40.0%) or tubal infertility (36.6%). After 1-4 IVF/ICSI treatments, including frozen embryo transfer, 56.7% of the women with stage III/IV endometriosis were pregnant and 40.3% gave birth. The corresponding values were 67.7/55.8% when endometriosis was stage I/II and 81.6/43.7% in the controls respectively. Stage III/IV endometriosis means a worse prognosis for IVF/ICSI treatments compared to milder stages or tubal factors. Lower implantation and multiple pregnancy rates offer some support to our practice to continue two embryo transfers in this group.

Reference

Kuivasaari P, Hippelainen M, Anttila M, Heinonen S. . Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod. 2005 Nov;20(11):3130-5. Epub 2005 Jul 8.

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