Promising Perinatal Outcome after Using a Simplified Low-Cost IVF Culture System Specifically Designed for Resource-Poor Countries.

BACKGROUND: Assisted reproductive techniques services are often not accessible to the majority of infertile couples in Low and Middle Income Countries (LMIC) due to high costs. Lowering IVF laboratory costs is a crucial step to make IVF affordable for a larger part of the world population. We developed a simplified culture system (SCS) which has proven to be effective, and the next step is to prove its safety. METHODS: Preterm birth (PTB) and low birthweight (LBW) of 176 singletons born after using the SCS, 105 after fresh embryo transfer (fresh ET), and 71 after frozen embryo transfer (frozen ET) were compared with all IVF/ICSI singletons born in Belgium between 2013 and 2018. When comparing our 105 SCS babies born after fresh ET with all Belgian babies born after conventional IVF only, we also adjusted for 7 risk factors known to influence perinatal outcome, namelythe mother's age, day of transfer, pituitary inhibition protocol, rank of cycles, number of oocytes retrieved, number of embryos transferred, and gender of the baby. FINDINGS: Before adjustment, we found a significantly higher PTB (10.2% vs. 3.8%, OR 2.852, 95% CI [1.042-7.803], p-value 0.0413) and LBW (9.8% vs. 2.9%, OR 3.692, 95% CI [1.163-11.721], p-value 0.0267) in the conventional IVF group versus SCS after fresh ET. After adjusting for seven risk parameters, these differences remained significant (PTB: OR 2.627, 95% CI [1.013-6.816], p-value 0.0471) and LBW: OR 3.267, 95% CI [1.118-9.549], p-value 0.0305). PTB and LBW between both groups was not significantly different for singletons born after frozen ET. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons in FRET cycles are very reassuring and significantly lower compared to babies born after conventional IVF in Belgium. Being aware of its effectiveness, our results offer a good perspective for SCS to become an important tool to implement low-cost IVF in LMIC.

Multiyear outcomes using sibling oocytes demonstrates safety and efficacy of a simplified culture system consistent with use in a low-cost IVF setting.

RESEARCH QUESTION: Can a novel closed simplified IVF culture system be used to achieve outcomes comparable to those obtained with intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: This analysis is part of a non-inferiority prospective study comparing ICSI and a simplified culture system (SCS) for gamete fertilization in a selected group of patients. According to protocol, sibling oocytes in intact cumulus-oocyte complexes were randomly distributed between ICSI and conventional insemination in the SCS. For women, selection criteria included being under 43 years of age and at least six eggs at retrieval. An inseminating motile sperm count ≥1 million was required. The primary outcome measure was ongoing pregnancy rate (>12 weeks) per cycle; secondary outcome measures included fertilization rate, miscarriage rate and implantation rate (ongoing pregnancy rate per embryo). RESULTS: From January 2016 until December 2019, 653 SCS/ICSI cycles were performed yielding a total of 7915 oocytes. The fertilization rate was 61.1% and 50.4% for SCS and ICSI (P < 0.0001), respectively. The ongoing pregnancy rate was 32.0% for SCS and 36.7% for ICSI (P = 0.27). Implantation rate was 30.6% for SCS and 34.4% for ICSI (P = 0.35). The miscarriage rate was 7.5% and 6.5% for SCS and ICSI, respectively (P = 0.75). CONCLUSION: No difference was found in ongoing pregnancy rate, implantation rate and the miscarriage rate between SCS and ICSI in this selected patient cohort.

Perinatal outcome of babies born after using a simplified IVF culture system versus ICSI with sibling oocytes: a prospective cohort study.

RESEARCH QUESTION: Is there a difference in perinatal outcome in the same patient cohort for babies conceived following randomization of sibling oocytes allocated to a simplified IVF culture system (SCS) or intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: The study compared the perinatal outcomes of 367 babies born from 1 January 2013 until 31 December 2020 after using split SCS and ICSI insemination of sibling oocytes in a selected group of normo-responsive women, excluding cases of severe male infertility. Primary outcome measures were preterm birth (PTB; <37 weeks' gestation), low birthweight (LBW; <2.5 kg) and small for gestational age (SGA) as a primary outcome parameter while secondary outcome measures included mean birthweight, mean gestational age, extreme prematurity (<32 weeks), very low birthweight (<1.5 kg), perinatal mortality, multiple pregnancy and Caesarean section rate. RESULTS: A total of 105 and 103 singleton babies were born after fresh embryo transfer (FRET) and 71 and 50 singletons after frozen embryo transfer (FET) in the SCS and ICSI groups, respectively. For babies born after FRET, the LBW rate was 2.9% (3/105) for SCS and 7.8% (8/103) for ICSI (P = 0.10). LBW occurred in 4.2% (3/71) and 0% (0/50) of babies born after the transfer of cryopreserved-thawed SCS and ICSI embryos, respectively (P = 0.14). The rate of PTB was 3.8% and 6.8% for SCS and ICSI in FRET cycles (P = 0.33), and 8.5% and 6.0% for SCS and ICSI in FET cycles (P = 0.62). One congenital malformation was found in the SCS FET group. CONCLUSION: There was no difference in perinatal outcome for singleton and twin babies born after SCS and ICSI.

Negative Impact of Elevated DNA Fragmentation and Human Papillomavirus (HPV) Presence in Sperm on the Outcome of Intra-Uterine Insemination (IUI).

We wanted to determine the sperm DNA fragmentation index (DFI) cutoff for clinical pregnancies in women receiving intra-uterine insemination (IUI) with this sperm and to assess the contribution of Human Papillomavirus (HPV) infection on sperm DNA damage and its impact on clinical pregnancies. Prospective non-interventional multi-center study with 161 infertile couples going through 209 cycles of IUI in hospital fertility centers in Flanders, Belgium. Measurement of DFI and HPV DNA with type specific quantitative PCRs (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) in sperm before its use in IUI. Clinical pregnancy (CP) rate was used as the outcome to analyze the impact on fertility outcome and to calculated the clinical cutoff value for DFI. A DFI criterion value of 26% was obtained by receiver operating characteristic (ROC) curve analysis. Couples with a male DFI > 26% had significantly less CPs than couples with DFI below 26% (OR 0.0326; 95% CI 0.0019 to 0.5400; p = 0.017). In sperm, HPV prevalence was 14.8%/IUI cycle. Sperm samples containing HPV had a significantly higher DFI compared to HPV negative sperm samples (29.8% vs. 20.9%; p = 0.011). When HPV-virions were present in sperm, no clinical pregnancies were observed. More than 1 in 5 of samples with normal semen parameters (17/78; 21.8%) had an elevated DFI or was HPV positive. Sperm DFI is a robust predictor of clinical pregnancies in women receiving IUI with this sperm. When DFI exceeds 26%, clinical pregnancies are less likely and in vitro fertilization techniques should be considered.

Motivations and attitudes of candidate sperm donors in Belgium.

OBJECTIVE: To study the motivation and attitudes of a candidate sperm donor population in Belgium. DESIGN: Anonymous survey. SETTING: Tertiary referral infertility center. PATIENT(S): One hundred candidate sperm donors applying to the center for a first semen analysis between April 2013 and March 2016. INTERVENTION(S): Invitation to complete an anonymous questionnaire. MAIN OUTCOME MEASURE(S): Demographic characteristics, recruitment methods, motivations and attitudes toward payment, donor anonymity, disclosure to offspring, donation to lesbian couples and single women, views on the donor children and social aspects of sperm donation. RESULT(S): The majority of our candidate donor population were older men with a partner who were donating sperm for altruistic reasons. The financial compensation was only an important motivational factor in 31% of the candidate sperm donors. Eighty-two percent of the men said they were willing to reveal nonidentifying information about themselves to donor offspring, but only 26% were willing to donate nonanonymously. The wish to receive certain information about the recipient family and the donor offspring was linked to men who had a partner and a child of their own. CONCLUSION(S): The wish to receive and donate information depends on the characteristics and beliefs of the candidate donors. Also, the donor's characteristics were linked to the acceptance of meeting the offspring in the future: the donors with a partner and donors who said they would donate without financial reimbursement were less willing to meet the donor offspring.

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.

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.

Self-operated endovaginal telemonitoring versus traditional monitoring of ovarian stimulation in assisted reproduction: an RCT.

STUDY QUESTION: Does self-operated endovaginal telemonitoring (SOET) of the ovarian stimulation phase in IVF/ICSI produce similar laboratory, clinical, patient reported and health-economic results as traditional monitoring (non-SOET)? SUMMARY ANSWER: SOET is not inferior to traditional monitoring (non-SOET). WHAT IS KNOWN ALREADY: Monitoring the follicular phase is needed to adapt gonadotrophin dose, detect threatening hyperstimulation and plan HCG administration. Currently, patients pay visits to care providers, entailing transportation costs and productivity loss. It stresses patients, partners, care providers and the environment. Patients living at great distance from centres have more difficult access to treatment. The logistics and stress during the follicular phase of assisted reproduction treatment (ART) is often an impediment for treatment. STUDY DESIGNS, SIZE, DURATION: The study was a non-inferiority RCT between SOET and non-SOET performed between February 2012 and October 2013. Sample size calculations of number of metaphase II (MII) oocytes (the primary outcome): 81 patients were needed in each study arm for sufficient statistical power. Block randomization was used with allocation concealment through electronic files. The first sonogram was requested after 5 days of stimulation, after that mostly every 2 days and with a daily sonograms at the end. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Inclusion criteria were age <41 years, undergoing ICSI, no poor response and having two ovaries. We used a small laptop with USB connected vaginal probe and developed a specific web site application. Sonographic training was given to all women at the initiation of a treatment attempt at the centre. The website contained demonstration material consisting of still images and video sequences, as well as written instructions regarding the use of the instrument and probe handling. In total, 185 eligible patients were recruited in four centres: 123 were randomized; 121 completed SOET (n = 59) or non-SOET (n = 62), and 62/185 (33%) eligible patients declined participation for various reasons. MAIN RESULTS AND THE ROLE OF CHANCE: Patient characteristics were comparable. The clinical results showed similar conception rates (P = 0.47) and ongoing pregnancy rates (SOET: 15/59 = 25%; non-SOET: 16/62 = 26%) (P = 1.00) were obtained. Similar numbers of follicles >15 mm diameter at oocyte retrieval (OR), ova at OR, MII oocytes, log2 MII oocytes, embryos available at transfer, top quality embryos and embryos frozen were obtained in the two groups, indicating non-inferiority of SOET monitoring. Regarding patient-reported outcomes, a significantly higher contentedness of patient and partner (P < 0.01), a higher feeling of empowerment, discretion and more active partner participation (P < 0.001) as well as a trend towards less stress (P = 0.06) were observed in the S versus the NS group. In the economic analysis, the use of SOET led to reduced productivity loss, lower transportation costs, and lower sonogram and consultation costs (all P < 0.001 but higher personnel cost than NS). LIMITATIONS, REASONS FOR CAUTION: The study was stopped (no further funding) before full sample size was reached. There were also a few cases of unexpected poor response, leading to a wider SD than anticipated in the power calculation. However, although the study was underpowered for these reasons, non-inferiority of SOET versus non-SOET was demonstrated. WIDER IMPLICATIONS OF THE FINDINGS: Home monitoring using SOET may provide a patient-centred alternative to the standard methods. ART sonograms can be made, and then sent to the care provider for analysis at any appropriate time and from anywhere if an internet connection is available. This approach offers several advantages for patients as well as care providers, including similar results to the traditional methods with less logistical stress and potentially bringing care to patients in poor resource settings. STUDY FUNDING/COMPETING INTERESTS: Supported by an IOF (industrial research fund) of Ghent University (full protocol available at iBiTech) and as a demonstration project of Flanders Care (Flemish Government). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: EC/2011/669 (Ghent University Hospital), B670201112232 (Belgian registration) and NCT01781143 (clinical trials number).

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.

Prevalence and concordance of HPV, HIV, and HSV-2 in heterosexual couples in Kigali, Rwanda.

BACKGROUND: In the absence of prospectively collected transmission data, the transmission potential of a sexually transmissible infection (STI) can be estimated by its proxy of concordance in sexual partners. Here we report concordance data of 3 viral STIs: human papillomavirus (HPV), HIV, and herpes simplex virus type 2 (HSV-2) among heterosexual couples in Kigali, Rwanda. METHODS: Cervical and penile HPV typing was performed among 166 community-sampled fertile couples in Kigali, Rwanda (median sampling interval 10 days (interquartile range: 5-36). HIV and HSV-2 serostatus, curable STIs, and sociobehavioral and clinical characteristics were also assessed. RESULTS: Concordance rates for all 3 viral STIs were higher than expected by chance alone. Positive concordance among couples was 25% for HSV-2, 15.7% for any HPV, 8.4% for high-risk (HR)-HPV, and 6% for HIV. HR-HPV prevalence among women and men was 19.9% and 26.5%, respectively. Partner's HIV status was more strongly associated with HR-HPV detection in men (OR: 8.5; confidence interval: 2.9-24.6) than in women (OR: 1.9; confidence interval 0.5-6.7). CONCLUSION: More than half of the couples were discordant for HIV, HPV, and/or HSV-2, indicating that prevention strategies directed to infected cases are important to protect their uninfected sexual partners.

Chlamydia trachomatis infection in fertile and subfertile women in Rwanda: prevalence and diagnostic significance of IgG and IgA antibodies testing.

BACKGROUND: In many developing countries, little is known about the prevalence of genital Chlamydia trachomatis infections and complications, such as infertility, thus preventing any policy from being formulated regarding screening for C. trachomatis of patients at risk for infertility. The objective of the present study was to determine the prevalence of C. trachomatis and evaluate the diagnostic utility of serological markers namely anti-C. trachomatis IgG and IgA antibodies in women attending an infertility clinic. METHODS: Serum and vaginal swab specimens of 303 women presenting with infertility to the infertility clinic of the Kigali University Teaching Hospital and 312 fertile controls who recently delivered were investigated. Two commercial species-specific ELISA were used to determine serum IgG and IgA antibodies to C. trachomatis and vaginal swabs specimens were tested by PCR. Hysterosalpingography (HSG) was performed in subfertile women. RESULTS: The PCR prevalence of C. trachomatis infection was relatively low and did not differ significantly among subfertile and fertile women (3.3 versus 3.8%). Similarly, no significant differences in overall prevalence rates of C. trachomatis IgG and IgA among both groups were observed. The only factor associated with C. trachomatis infection in our study population was age <25 years. The seroprevalence of IgG in both assays (86.4% for ANILabsystems and 90.9% for Vircell) was significantly higher in the group of PCR C. trachomatis-positive women compared with that of PCR-negative women. Evidence of tubal pathology identified by HSG was found in 185 patients in the subfertile group (67.8%). All the serological markers measured in this study had very low sensitivities and negative predictive values in predicting tubal pathology. The specificities for ANILabsystems IgG, Vircell IgG, Anilabsystem IgA and positive C. trachomatis DNA to predict tubal pathology were 84, 86, 95 and 98%, respectively, whereas their respective positive predictive values were 73, 76, 81 and 80%. CONCLUSIONS: The prevalence of C. trachomatis in our study population in Rwanda appears to be low and women aged <25 years are more likely to have genital infection with C. trachomatis. Since serological testing for Chlamydia shows an excellent negative predictive value for lower genital tract infection, specific peptide-based serological assays may be of use for screening in low prevalence settings. Our data suggest that C. trachomatis is not the primary pathogen responsible for tubal pathology in Rwandan women.

Evaluation of a new multiplex polymerase chain reaction assay STDFinder for the simultaneous detection of 7 sexually transmitted disease pathogens.

We evaluated a new multiplex polymerase chain reaction (mPCR), "STDFinder assay", a novel multiplex ligation-dependent probe amplification (MLPA) assay for the simultaneous detection of 7 clinically relevant pathogens of STDs, i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, Treponema pallidum, and herpes simplex virus type 1 and 2 (HSV-1 and HSV-2). An internal amplification control was included in the mPCR reaction. The limits of detection for the STDFinder assay varied among the 7 target organisms from 1 to 20 copies per MLPA assay. There were no cross-reactions among any of the probes. Two hundred and forty-two vaginal swabs and an additional 80 specimens with known results for N. gonorrhoeae and C. trachomatis, obtained from infertile women seen at an infertility research clinic at the Kigali Teaching Hospital in Rwanda, were tested by STDFinder assay and the results were confirmed by single real-time PCR using different species-specific targets. Compared to the reference standard, the STDFinder assay showed specificities and sensitivities of 100% and 100%, respectively, for N. gonorrhoeae, C. trachomatis, and M. genitalium; 90.2% and 100%, respectively, for Trichomonas vaginalis; and 96.1% and 100%, respectively, for HSV-2. No specimen was found to be positive for HSV-1 by either the STDFinder assay or the comparator method. Similarly, the sensitivity for Treponema pallidum could not be calculated due to the absence of any Treponema pallidum-positive samples. In conclusion, the STDFinder assays have comparable clinical sensitivity to the conventional mono and duplex real-time PCR assay and are suitable for the routine detection of a broad spectrum of these STDs at relatively low cost due to multiplexing.

The risk factor profile of women with secondary infertility: an unmatched case-control study in Kigali, Rwanda.

BACKGROUND: Secondary infertility is a common, preventable but neglected reproductive health problem in resource-poor countries. This study examines the association of past sexually transmitted infections (STIs) including HIV, bacterial vaginosis (BV) and factors in the obstetric history with secondary infertility and their relative contributions to secondary infertility. METHODS: Between November 2007 and May 2009 a research infertility clinic was set up at the Kigali University Teaching Hospital in Rwanda. Cases were defined as sexually-active women aged 21-45 years presenting with secondary infertility (n = 177), and controls as multiparous women in the same age groups who recently delivered (n = 219). Participants were interviewed about socio-demographic characteristics and obstetric history using structured questionnaires, and were tested for HIV and reproductive tract infections (RTIs). RESULTS: Risk factors in the obstetric history for secondary infertility were lack of prenatal care in the last pregnancy, the first pregnancy before the age of 21 years, a history of unwanted pregnancy, a pregnancy with other than current partner, an adverse pregnancy outcome, stillbirth, postpartum infection and curettage. Presence of HIV, herpes simplex virus type 2 (HSV-2), or Treponema pallidum antibodies, and bacterial vaginosis (BV), were significantly more common in women in secondary infertile relationships than those in fertile relationships. The population attributable fractions (PAF%) for obstetric events, HIV, other (STIs), and BV were 25%, 30%, 27%, and 14% respectively. CONCLUSIONS: The main finding of this study is that obstetric events, HIV and other STIs contribute approximately equally to secondary infertility in Rwanda. Scaling up of HIV/STI prevention, increased access to family planning services, improvement of prenatal and obstetric care and reduction of stillbirth and infant mortality rates are all likely to decrease secondary infertility in sub-Saharan Africa.

Results of infertility investigations and follow-up among 312 infertile women and their partners in Kigali, Rwanda.

The objectives of this study were to assess the outcome of infertility investigations and an 18-month follow-up of 312 infertile women and their partners in Rwanda. Between November 2007 and May 2009, an infertility research clinic was opened. Infertile couples received basic infertility investigations, the available treatment was provided and couples were followed up over an 18-month period. The infertility remained unexplained in 3%, was due to a female factor in 31%, due to a male factor in 16% or due to a combination of male and female causes in 50% of fully investigated couples (n = 224). A tubal factor was found in 69% of women, a male factor in 64% of men. Predictors for tubal infertility in women included a history of high-risk sexual behaviour, HIV infection and a history of sexually transmitted infection (STI) symptoms in the male partner. After 12-18 months of follow-up, 40 pregnancies (16%) had occurred in 244 women. Our study shows high rates of tubal and male factor infertility in Rwanda. Pregnancy rates were low after conventional therapy. In order to provide effective and affordable treatment for infertility in resource-poor countries the development of low-cost assisted reproductive technologies are needed.

HIV infection and sexual behaviour in primary and secondary infertile relationships: a case--control study in Kigali, Rwanda.

OBJECTIVE: To compare the prevalence of sexually transmitted infections (STIs) (including HIV) and of high-risk sexual behaviour in the following three groups: primary infertile relationships, secondary infertile relationships and fertile relationships. Primary infertility is here defined as never having conceived before, secondary infertility as infertility subsequent to having conceived at least once. DESIGN: Unmatched case--control study. METHODS: Sexually active infertile women aged 21-45 years presenting at an infertility clinic of the Kigali Teaching Hospital, Rwanda and their male partners were invited to participate. Fertile controls who had recently delivered were recruited from the community. In a face-to-face interview, participants were asked about sociodemographic characteristics and their sexual behaviours, and tested for HIV and STIs. RESULTS: Between November 2007 and May 2009, 312 women and 254 partners in infertile relationships and 312 women and 189 partners in fertile relationships were enrolled. Involvement in a secondary infertile relationship was associated with HIV infection after adjusting for sociodemographic covariates for women (adjusted OR (AOR) = 4.03, 95% CI 2.4 to 6.7) and for men (AOR = 3.3, 95% CI 1.8 to 6.4). Involvement in a primary infertile relationship, however, was not. Secondary infertile women were more likely to have engaged in risky sexual behaviour during their lifetime compared with primary infertile and fertile women. Men in primary and secondary infertile relationships more often reported multiple partners in the past year (AOR = 5.4, 95% CI 2.2 to 12.7; AOR = 7.1, 95% CI 3.2 to 15.8, respectively). CONCLUSIONS: Increased HIV prevalence and risky sexual behaviour among infertile couples is driven by secondary infertility. Infertile couples, and especially those with secondary infertility, should be targeted for HIV prevention programmes and their fertility problems should be addressed.

Improved access increases postpartum uptake of contraceptive implants among HIV-positive women in Rwanda.

BACKGROUND: Long-acting reversible contraceptives (LARCs) and sterilisation are the most cost-effective methods of contraception but are rarely used in sub-Saharan Africa partly due to limited access. STUDY DESIGN: HIV-positive pregnant women attending two urban clinics in Rwanda were followed prospectively in a perinatal HIV transmission cohort study. Women attending one clinic were referred to public family planning (FP) services for all contraceptive methods (Site A) and women attending the other clinic (Site B) were offered implants and intrauterine devices (IUDs) on-site. RESULTS: Fifty three percent of the pregnant women reported an intention to use a LARC or to be sterilised after delivery. The uptake of implants was significantly higher at Site B (38%) than at Site A (6%). The IUD uptake was extremely low at both sites (2%). Twenty-eight of the 39 women at Site B who had intended to start using a LARC actually did so as compared to only one of 23 at Site A. CONCLUSION: When access to LARC was provided, a substantial number of HIV-positive women started using hormonal implants, but not IUDs, in the postpartum period. HIV and FP services should consider improving access to implants to reduce the number of unintended pregnancies.