Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?

Study Question: Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles?

Summary Answer: Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles.

What Is Already Known: For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth.

Tubal flushing with oil- or water-based contrast medium: can we identify markers that indicate treatment benefit?

Study Question: Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium?

Summary Answer: In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple.

What Is Known Already: We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium.

Study Design Size Duration: We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based ( = 557) or water-based ( = 562) contrast medium.

Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis: study protocol of a non-inferiority randomized controlled trial.

Study Questions: The primary objective is to investigate if continuous use of oral contraceptives is non-inferior compared to long-term pituitary desensitization with a GnRH agonist prior to IVF/ICSI in patients with moderate to severe endometriosis with regard to treatment efficacy. Secondary objectives concern treatment safety and cost-effectiveness.

What Is Known Already: Long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis.

The therapeutic effect of hysterosalpingography in couples with unexplained subfertility: a post-hoc analysis of a prospective multi-centre cohort study.

Research Question: Hysterosalpingography (HSG) with an oil-based contrast has been shown to increase ongoing pregnancy rates compared with HSG with water-based contrast, but it remains unclear if an effect of HSG occurs compared with no HSG.

Design: A secondary data-analysis of a prospective cohort study among 4556 couples that presented with unexplained subfertility in 38 clinics in the Netherlands between January 2002 and December 2004. A time-varying Cox regression with inverse probability of treatment weighing was used to analyse ongoing pregnancy rates in women after undergoing the HSG procedure (with the use of either water- or oil-based contrast media) compared with women who did not undergo HSG.

Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure: a cost-effectiveness analysis.

Study Question: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC?

Summary Answer: Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC.

What Is Known Already: In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown.

Oil-based or water-based contrast for hysterosalpingography in infertile women: a cost-effectiveness analysis of a randomized controlled trial.

Objective: To determine the cost effectiveness of the use of oil-based versus water-based contrast in infertile women undergoing hysterosalpingography (HSG).

Design: Economic evaluation alongside a multicenter randomized trial.

Setting: Hospitals.

Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.

Background: In many countries, clomifene citrate is the treatment of first choice in women with normogonadotropic anovulation (ie, absent or irregular ovulation). If these women ovulate but do not conceive after several cycles with clomifene citrate, medication is usually switched to gonadotrophins, with or without intrauterine insemination. We aimed to assess whether switching to gonadotrophins is more effective than continuing clomifene citrate, and whether intrauterine insemination is more effective than intercourse.

Women's perspectives on ovulation induction with or without IUI as treatment for normogonadotrophic anovulation: a discrete choice experiment.

Study Question: What are the treatment preferences of women with normogonadotrophic anovulation treated with ovulation induction with or without intrauterine insemination (IUI)?

Summary Answer: Women with normogonadotrophic anovulation differ in their treatment preference; half of them base their preference on the lowest burden and half of them on the highest effectiveness.

What Is Known Already: Common treatments for anovulatory women who wish to conceive are ovulation induction using clomiphene citrate or letrozole taken in tablet form or with injections containing gonadotrophins, all optionally combined with IUI. Patient preferences for these alternatives have not yet been examined in these women.

Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.

Background: Pregnancy rates among infertile women have been reported to increase after hysterosalpingography, but it is unclear whether the type of contrast medium used (oil-based or water-soluble contrast) influences this potential therapeutic effect.

Methods: We performed a multicenter, randomized trial in 27 hospitals in the Netherlands in which infertile women who were undergoing hysterosalpingography were randomly assigned to undergo this procedure with the use of oil-based or water-based contrast. Subsequently, couples received expectant management or the women underwent intrauterine insemination.

Cost-effectiveness of single versus double embryo transfer in IVF in relation to female age.

Objective: To evaluate the cost-effectiveness of single embryo transfer followed by an additional frozen-thawed single embryo transfer, if more embryos are available, as compared to double embryo transfer in relation to female age.

Study Design: We used a decision tree model to evaluate the costs from a healthcare provider perspective and the pregnancy rates of two embryo transfer policies: one fresh single embryo transfer followed by an additional frozen-thawed single embryo transfer, if more embryos are available (strategy I), and double embryo transfer (strategy II). The analysis was performed on an intention-to-treat basis.

A revised prediction model for natural conception.

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability.

The effectiveness of intrauterine insemination: A matched cohort study.

Objective: To study the effectiveness of an intrauterine insemination (IUI) program compared to no treatment in subfertile couples with unexplained subfertility and a poor prognosis on natural conception.

Study Design: A retrospective matched cohort study in which ongoing pregnancy rates in 72 couples who voluntarily dropped out of treatment with IUI were compared to ongoing pregnancy rates in 144 couples who continued treatment with IUI. Couples with unexplained subfertility, mild male subfertility or cervical factor subfertility who started treatment with IUI between January 2000 and December 2008 were included.

Endometrial thickness in women undergoing IUI with ovarian stimulation. How thick is too thin? A systematic review and meta-analysis.

Study Question: Is pre-ovulatory endometrial thickness (EMT) in women with unexplained subfertility undergoing IUI with ovarian stimulation (OS) associated with pregnancy chances?

Summary Answer: We found no evidence for an association between EMT and pregnancy chances.

What Is Known Already: It has been suggested that OS with clomiphene citrate (CC) results in a lower EMT than with gonadotrophins or aromatase inhibitors, but the clinical consequences in terms of pregnancy are unclear.

Study Design, Size, Duration: We performed a systematic review and meta-analysis of studies comparing CC, gonadotrophins or aromatase inhibitors in an IUI program reporting on EMT and pregnancy rates in women with unexplained subfertility.

Natural conception: repeated predictions over time.

Study Question: How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility?

Summary Answer: We developed a dynamic prediction model that can make repeated predictions over time for couples with unexplained subfertility that underwent a fertility workup at a fertility clinic.

What Is Known Already: The most frequently used prediction model for natural conception (the 'Hunault model') estimates the probability of natural conception only once per couple, that is, after completion of the fertility workup. This model cannot be used for a second or third time for couples who wish to know their renewed chances after a certain period of expectant management.

Reporting multiple cycles in trials on medically assisted reproduction.

Trials assessing effectiveness in medically assisted reproduction (MAR) should aim to study the desired effect over multiple cycles, as this reflects clinical practice and captures the relevant perspective for the couple. The aim of this study was to assess the extent to which multiple cycles are reported in MAR trials. A sample of randomized controlled trials (RCT) was collected on MAR, published in four time periods, in 11 pre-specified peer-reviewed journals; 253 trials were included: 196 on IVF, 37 on intrauterine insemination and 20 on ovulation induction.

Dropout rates in couples undergoing in vitro fertilization and intrauterine insemination.

Objective: To compare dropout rates in couples undergoing conventional in vitro fertilization with single embryo transfer (IVF-SET), in vitro fertilization in a modified natural cycle (IVF-MNC) or intrauterine insemination with ovarian stimulation (IUI-OS).

Study Design: Secondary analysis of a multicentre randomized controlled trial between January 2009 and February 2012. 602 couples with unexplained or mild male subfertility, allocated to IVF-SET (N=201), IVF-MNC (N=194) and IUI-OS (N=207).

Hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy as a treatment for hydrosalpinges prior to IVF or ICSI: an RCT.

Study Question: Does hysteroscopic proximal tubal occlusion by intratubal devices as a treatment for hydrosalpinges result in comparable ongoing pregnancy rates following IVF/ICSI when compared with laparoscopic salpingectomy?

Summary Answer: Hysteroscopic proximal tubal occlusion by intratubal devices is inferior to laparoscopic salpingectomy in the treatment of hydrosalpinges in women undergoing IVF/ICSI with respect to ongoing pregnancy rates.

What Is Known Already: It is known that women with hydrosalpinges undergoing IVF have poorer pregnancy outcomes compared with women with other forms of tubal infertility. In these women, both laparoscopic salpingectomy and laparoscopic proximal tubal ligation are known to improve IVF outcomes.

Embryo Transfer with Controlled Injection Speed to Increase Pregnancy Rates: A Randomized Controlled Trial.

Background/aims: Catheter injection speed affects depth and placement of the embryo into the uterine cavity and is shown to be highly variable in, and between, subjects in a manually performed embryo transfer. In an effort to standardize the injection speed during embryo transfer, we developed an automated transfer pump: the pump-regulated embryo transfer (PRET) device. In this randomized controlled trial, we aimed to investigate if standardization of the injection speed and pressure with this PRET results in a better controlled positioning of the transferred embryo(s).

Reducing Inter-Laboratory Differences between Semen Analyses Using Z Score and Regression Transformations.

Background: Standardization of the semen analysis may improve reproducibility. We assessed variability between laboratories in semen analyses and evaluated whether a transformation using Z scores and regression statistics was able to reduce this variability.

Materials And Methods: We performed a retrospective cohort study.

Does the postcoital test predict pregnancy in WHO II anovulatory women? A prospective cohort study.

Objective: To assess the capacity of the postcoital test (PCT) to predict pregnancy in WHO II anovulatory women who are ovulatory on clomiphene citrate (CC). In these women, an abnormal PCT result could be associated with lower pregnancy chances, but this has never been proven or refuted.

Study Design: Prospective cohort study was performed between December 2009 and September 2012 for all women who started ovulation induction with CC in one university clinic and two teaching hospitals in the Netherlands.

Does polycystic ovary syndrome affect cognition? A functional magnetic resonance imaging study exploring working memory.

Objective: To study effects of overexposure to androgens and subsequent antiandrogenic treatment on brain activity during working memory processes in women with polycystic ovary syndrome (PCOS).

Design: In this longitudinal study, working memory function was evaluated with the use of functional magnetic resonance imaging (MRI) in women with PCOS before and after antiandrogenic treatment.

Setting: Department of reproductive medicine, university medical center.

Presence of human papillomavirus in semen in relation to semen quality.

Study Question: Is the presence of human papillomavirus (HPV) in semen associated with impairment of semen quality?

Summary Answer: In a large cohort of males seeking fertility evaluation, no associations were observed between seminal HPV presence and semen parameters.

What Is Known Already: HPV is commonly detected in semen samples. Whether the presence of HPV is related to impairment of semen quality, remains unclear.

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome.

Objective: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy.

Mid-pregnancy, perinatal, and neonatal reproductive endocrinology: a prospective cohort study in twins and singleton control subjects.

Objective: To answer the questions: Are perinatal reproductive hormone profiles different in case of a twin compared with a singleton pregnancy? Are reproductive endocrine profiles of twin girls influenced by their male co-twin and vice versa?

Design: Prospective cohort study from January 2004 to October 2009.

Setting: Not applicable.

Patient(s): A total of 204 mothers of twins and 248 singleton control subjects, aged >18 years, pregnant with a twin or singleton and no endocrine disease or malignancy.

Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

Study Question: What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?.

Summary Answer: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy.