Low-dose human menopausal gonadotrophin versus clomiphene citrate in subfertile couples treated with intrauterine insemination: a randomized controlled trial.

STUDY QUESTION: Can controlled ovarian stimulation with low-dose human menopausal gonadotrophin (hMG) improve the clinical pregnancy rate when compared with ovarian stimulation with clomiphene citrate (CC) in an intrauterine insemination (IUI) programme for subfertile couples? SUMMARY ANSWER: Ovarian stimulation with low-dose hMG is superior to CC in IUI cycles with respect to clinical pregnancy rate. WHAT IS KNOWN ALREADY: IUI after ovarian stimulation is an effective treatment for mild male subfertility, unexplained subfertility and minimal-mild endometriosis, but it is unclear which medication for ovarian stimulation is more effective. STUDY DESIGN, SIZE, DURATION: A total of 330 women scheduled for IUI during 657 cycles (September 2004-December 2011) were enrolled in an open-label randomized clinical trial to ovarian stimulation with low-dose hMG subcutaneous (n = 334, 37.5-75 IU per day) or CC per oral (n = 323, 50 mg/day from Day 3-7). Assuming a difference of 10% in 'clinical pregnancy with positive fetal heart beat', we needed 219 cycles per group (alpha-error 0.05, power 0.80). PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied subfertile couples with mild male subfertility, unexplained subfertility or minimal-mild endometriosis. Further inclusion criteria were failure to conceive for ≥12 months, female age ≤42 years, at least one patent Fallopian tube and a total motility count (TMC) ≥5.0 million spermatozoa after capacitation. The primary end-point was clinical pregnancy. Analysis was by intention to treat and controlled for the presence of multiple measures, as one couple could have more randomizations in multiple cycles. Linear mixed models were used for continuous measures. For binary outcomes we estimated the relative risk using a Poisson model with log link and using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE: When compared with ovarian stimulation with CC, hMG stimulation was characterized by a higher clinical pregnancy rate (hMG 48/334 (14.4%) versus CC 29/323 (9.0%), relative risk (RR) 1.6 (95% confidence interval (CI) 1.1-2.4)), higher live birth rate (hMG 46/334 (13.8%) versus CC 28/323 (8.7%), RR 1.6 (95% CI 1.0-2.4)), low and comparable multiple live birth rate (hMG 3/46 (6.5%) versus CC 1/28 (3.6%), P > 0.99), lower number of preovulatory follicles (hMG 1.2 versus CC 1.5, P < 0.001), increased endometrial thickness (hMG 8.5 mm versus CC 7.5 mm, P < 0.001), and a lower cancellation rate per started cycle (hMG 15/322 (4.7%) versus CC 46/298 (15.4%), P < 0.001). LIMITATIONS, REASONS FOR CAUTION: We randomized patients at a cycle level, and not at a strategy over multiple cycles. WIDER IMPLICATIONS OF THE FINDINGS: This study showed better reproductive outcome after ovarian stimulation with low-dose gonadotrophins. A health economic analysis of our data is planned to test the hypothesis that ovarian stimulation with low-dose hMG combined with IUI is associated with increased cost-effectiveness when compared with ovarian stimulation with CC. STUDY FUNDING/ COMPETING INTERESTS: T.M.D. and K.P. were supported by the Clinical Research Foundation of UZ Leuven, Belgium. This study was also supported by the Ferring company (Copenhagen, Denmark) which provide free medication (Menopur) required for the group of patients who were randomized in the hMG COS group. The Ferring company was not involved in the study design, data analysis, writing and submission of the paper. TRIAL REGISTRATION NUMBER: NCT01569945 (ClinicalTrials.gov).

The type of catheter has no impact on the pregnancy rate after intrauterine insemination: a randomized study.

BACKGROUND: This study was done to test the hypothesis that intrauterine insemination (IUI) using a soft-tip catheter results in a higher live birth rate than IUI using a hard-tip catheter. METHODS: Five hundred and forty patients were randomized into those inseminated with a soft-tip catheter (group 1, n = 267) and those inseminated with a hard-tip catheter (group 2, n = 269). Four patients were excluded. Main outcome measures included pregnancy rate and live birth rate per cycle. RESULTS: Both groups were similar with regard to female age, duration of infertility, ovarian stimulation and sperm quality. No significant differences were observed between group 1 and group 2 regarding clinical pregnancy rate per cycle (20 versus 19%), live birth rate per cycle (15 versus 14%), multiple live birth rate per cycle (4 versus 6%) and multiple live birth per total of live births (5 versus 8%, overall 6%), respectively. CONCLUSION: Our hypothesis that IUI using a soft tip catheter results in a higher live birth rate per cycle than IUI using a hard-tip catheter was not confirmed in this study. Multiple live birth rate after treatment with low-dose gonadotrophins and IUI can be kept low (6%).

Endometriosis and subfertility treatment: a review.

The aim of this article is to present a review on the influence of endometriosis on assisted reproductive techniques (ART), as well as on the influence of ART on endometriosis. Based on recent literature, this article will try to answer the following questions: 1) Does endometriosis change the success rate of ovulation induction (OI), intrauterine insemination (IUI) and in vitro fertilisation (IVF) and does previous chirurgical treatment of endometriosis change the success rate of OI, IUI and IVF? 2) Do ART alter the course of the disease? In order to answer these questions, we based ourselves on the following recent guidelines and reviews by reknown experts on endometriosis: the ESHRE Guideline for the Diagnosis and Treatment of Endometriosis, The Practice Committee of the American Society for Reproductive Medicine: Endometriosis and Fertility; a recent review paper on the relationship between endometriosis and subfertility and a recent meta-analysis on the relationship between endometriosis and ART. This review was then completed using more recent papers, published on PubMed as well as background articles, important references and own research papers presented at international meetings. The pregnancy rate after OI, IUI and IVF is decreased in women with endometriosis when compared to controls. The effect of previous surgery for endometriosis is unclear, due to great lack of standardised studies using well defined operation techniques and patient groups. The effect of ART on the spontaneous evolution and recurrence rate of endometriosis has hardly been studied. The presence of endometriosis has a negative effect on the pregnancy rate after ART. It is unclear if surgical treatment prior to ART may increase the pregnancy rate after ART. It is also unclear if ART is a risk factor for recurrence/progression of endometriosis.

A case report of unusual complication of myomatous uterus in pregnancy: spontaneous perforation of myoma after red degeneration.

An unusual complication of myomatous uterus in pregnancy is presented. It shows spontaneous perforation of a myoma after red degeneration, presenting as an acute abdomen. To our knowledge spontaneous perforation of a necrotising leiomyoma has not been reported earlier. A review of the literature is given.