Nathalie Dhont

Semen quality and prediction of IUI success in male subfertility: a systematic review

Many variables may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample. A literature search was performed to investigate the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved and/or the cut-off values reaching substantial discriminative performance in an IUI programme. A search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers. Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were analysed. Sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value ⩾5% normal morphology; (iii) total motile sperm count in the native sperm sample: cut-off value of 5-10 million; and (iv) total motility in the native sperm sample: threshold value of 30%. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. More prospective cohort trials and prospective randomized trials investigating the predictive value of semen parameters on IUI outcome are urgently needed. It is generally believed that intrauterine insemination (IUI) with homologous semen should be a first-choice treatment to more invasive and expensive techniques of assisted reproduction in cases of cervical, unexplained and moderate male factor subfertility. The rationale for the use of artificial insemination is to increase gamete density at the site of fertilization. Scientific validation of this strategy is difficult because literature is rather confusing and inconclusive. Many variables may influence success rates after IUI treatment procedures. It seems logical that sperm quality has to be one of the main determinants to predict IUI success. Clinical practice would benefit from the establishment of threshold levels for sperm parameters above which IUI pregnancy outcome is significantly improved and below which a successful outcome is unlikely. We performed a literature search to investigate if such threshold levels are known. Most striking were the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies. The four sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value >4% normal morphology; (iii) total motile sperm count in native sperm sample: cut-off value of 5-10 million; and (iv) total motility in native sperm sample: threshold value of 30%. This review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate.

First births with a simplified culture system for clinical IVF and embryo transfer

This study reports the outcome results from a pilot clinical trial using a simplified laboratory method for human IVF. This system reproducibly generates de novo the atmospheric and culture conditions that support normal fertilization and preimplantation embryogenesis to the hatched blastocyst stage without the need for specialized medical-grade gases or equipment. Development from insemination to the hatched blastocyst stage occurs undisturbed in a completely closed system that enables timed performance assessments for embryo selection in situ that, in this study, involved single-embryo transfers on day 3. With the simplified culture system, 8/23 embryos implanted, one miscarried at 8weeks of gestation and seven healthy babies have been born. The methodology and results are discussed with regard to how this simplified system can be adopted worldwide to meet the growing need for accessible and affordable IVF. A common notion concerning the demographics of infertility is that it is largely a phenomenon associated with developed countries, where infertility treatments are commonplace. In fact, most infertile couples reside in developing/low-resource countries where infertility diagnosis and treatment is nonexistent, inaccessible or unaffordable by the vast majority of young men and women in need. The irony of this situation is that bilateral tubal occlusions, for which IVF was originally indicated and is the most effective treatment, is by far the most common cause of their infertility. We have addressed one aspect of this issue, the IVF laboratory, as part of a wider effort by the Walking Egg Project to design and establish small, dedicated centres in developing countries to provide assisted reproduction technologies that are affordable and accessible to a wider proportion of the population in need. The methods for conventional IVF designed to addresses tubal obstructions are relatively simple and free of complex instrumentation and the highly developed infrastructure common to high-resource centres. This simplified IVF system self-generates culture conditions in a closed system. After prolonged preclinical testing, a pilot clinical study was initiated in 2012 in Genk, Belgium. The findings suggest that a significant first step has been achieved in the effort to bring advanced assisted reproduction to developed countries using a low-resource but highly effective IVF system capable of bringing modern reproductive medicine to infertile couples in low-resource societies.

Predictive value of different covariates influencing pregnancy rate following intrauterine insemination with homologous semen: a prospective cohort study

The aim was to examine the value of different covariates in the prediction of intrauterine insemination (IUI) success. Between July 2011 and September 2015, data from 1401 IUI cycles with homologous semen in 556 couples were collected prospectively, by questionnaire, in a tertiary referral infertility centre. Statistical analysis was performed using generalized estimating equations (GEEs). GEEs were used instead of an ordinary logistic regression model to take into account the correlation between observations from the same person. The primary outcome parameter was clinical pregnancy rate (CPR), confirmed with a gestational sac and fetal heartbeat on ultrasonography at 7-8 weeks. An overall CPR of 9.5% per cycle was observed. Univariate statistical analysis revealed female and male age, male smoking, female body mass index, ovarian stimulation and inseminating motile count (IMC) as covariates significantly influencing CPR per cycle. Multivariate GEE analysis revealed that the only valuable prognostic covariates included female age, male smoking and infertility status (i.e. primary/secondary infertility). IMC showed a significant curvilinear relationship, with first an increase and then a decrease in pregnancy rate.

Predictive factors influencing pregnancy rates after intrauterine insemination with frozen donor semen: a prospective cohort study

The extent to which certain parameters can influence pregnancy rates after intrauterine insemination with frozen donor semen was examined prospectively. Between July 2011 and September 2015, 402 women received 1264 IUI cycles with frozen donor semen in a tertiary referral infertility centre. A case report form was used to collect data prospectively. The primary outcome measure was clinical pregnancy rate (CPR), confirmed by detection of a gestational sac and fetal heartbeat using ultrasonography at 7-8 weeks of gestation. Statistical analysis was carried out using generalized estimating equations (GEE) to account for the correlation between observations from the same patient. Overall, CPR per cycle was 17.2%. Multivariate GEE analysis revealed the following parameters as predictive for a successful pregnancy outcome: female age (P = 0.0003), non-smoking or smoking fewer than 15 cigarettes a day (P = 0.0470 and P = 0.0235, respectively), secondary infertility (P = 0.0062), low progesterone levels at day zero of the cycle (P = 0.0164) and use of ovarian stimulation with HMG and recombinant FSH compared with clomiphene citrate and natural cycle (P = 0.0006 and P = 0.0004, respectively). These parameters were the most important factors influencing the success rate in a sperm donation programme.