Male vitamin D status and male factor infertility.

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.

Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination.

OBJECTIVE: To study the influence of human papillomavirus (HPV) virions present in different sperm fractions of male partners of women undergoing IUI on fertility outcome. DESIGN: Prospective noninterventional multicenter study. SETTING: Inpatient hospital fertility centers. PATIENT(S): Seven hundred thirty-two infertile couples undergoing 1,753 IUI cycles with capacitated sperm. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Biochemical and clinical pregnancy rate in IUI cycles with HPV-positive or HPV-negative semen. RESULT(S): Five hundred seventy-three infertile couples undergoing 1,362 IUI cycles were enrolled. Work-up of the 1,362 sperm samples that were used for IUI generated 3,444 separate sperm fractions. Each of the sperm fractions was tested with quantitative polymerase chain reaction for 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68). HPV prevalence in sperm was 12.5%/IUI cycle. When infectious HPV virions were detected in sperm, a significant decrease in clinical pregnancies was observed when compared with HPV-negative cycles (2.9% vs. 11.1 %/cycle). Above a ratio of 0.66 HPV virions/spermatozoon no pregnancies occurred (sensitivity 100%, specificity 32.5%). CONCLUSION(S): Women inseminated with HPV-positive sperm had 4 times fewer clinical pregnancies compared with women who had HPV-negative partners. Detection of HPV virions in sperm is associated with a negative IUI outcome and should be part of routine examination and counseling of infertile couples. EUROPEAN CLINICAL TRIALS DATABASE NUMBER: 2017-004791-56.

Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population.

OBJECTIVE: To determine whether men with unexplained infertility and low total T (TT) have abnormal spermatogenesis and lower fecundity. DESIGN: Secondary analysis of the prospective, randomized, multicenter clinical trial, Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS). SETTING: Infertility clinics. PATIENT(S): Nine hundred couples with unexplained infertility enrolled in AMIGOS. Semen analysis with an ejaculate of at least 5 million total motile sperm was required for enrollment. For inclusion in this secondary analysis, a fasting TT was required. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression, adjusted for age and body mass index, assessed the association between low TT (defined as <264 ng/dL), semen parameters, and pregnancy outcome. RESULT(S): Seven hundred eighty-one men (mean age, 34.2 ± 5.7 years) with a median (interquartile range) TT of 411 (318-520) ng/dL were included. Men with TT <264 ng/dL were less likely to have normal (≥4% strict Kruger) morphology (unadjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34, 0.92; adjusted OR, 0.59; 95% CI, 0.35, 0.99). There was no association between low TT and semen volume < 1.5 mL, sperm concentration < 15 × 106/mL, or motility < 40%. Among couples whose male partner had low TT, 21 (18.8%) had a live birth, compared with 184 (27.5%) live births in couples with a male partner having TT > 264 ng/dL. The odds of live birth decreased by 40% in couples whose male partner had low TT (unadjusted OR, 0.60; 95% CI, 0.36, 1.00; adjusted OR, 0.65; 95% CI, 0.38, 1.12). CONCLUSION(S): In couples with unexplained infertility, low TT in the male partner was associated with abnormal sperm morphology and lower live birth rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.

Risk of pelvic inflammatory disease after intrauterine insemination: a systematic review.

The aim of this study was to ascertain the incidence of pelvic inflammatory disease (PID) after intrauterine insemination (IUI). A systematic review was conducted using three different approaches: a search of IUI registries; a search of published meta-analyses; and a search of prospective randomized trials. Search terms were 'IUI', 'complications', 'infection' and 'PID'. Two IUI registers were identified that met the inclusion criteria, totalling 365,874 cycles, with 57 PID cases being reported. The post-IUI PID rate was 0.16/1000 (95% CI 0.2 to 0.3/1000). The frequency was higher in husband sperm cycles (0.21/1000) (28/135,839) than in donor sperm cycles (0.03/1000) (1/33,712) (P < 0.05; OR 6.95). Nineteen meta-analyses were retrieved, which included 156 trials, totalling 43,048 cycles, with no PID case being reported. Seventeen prospective clinical trials published between 2013 and 2014 were identified, totalling 4968 cycles; no PID case was reported. The reported rate of post-IUI clinical PID is low (0.16/1000), about 40% higher than reported in the general population of women during their reproductive life. No antibiotic prophylaxis should be recommended unless there is an associated risk factor.

Replacing IUI with IVF for initial treatment of unexplained infertility: why this NICE recommendation is cause for concern.

The latest guidelines from the National Institute for Health and Care Excellence (NICE) for assisted conception recommend that people experiencing unexplained infertility should no longer be offered stimulated intra-uterine insemination (IUI) as a first-line treatment, but rather be directed towards IVF or alternatively be left to expectant management. NICE has acknowledged that the cited evidence leading to this decision was not sufficiently robust. As such, we are concerned that accordance with these new NICE guidelines may result in people with no identifiable cause of their infertility being prematurely referred for IVF treatment. Since IVF constitutes a more invasive and expensive treatment process, which also represents an additional and unnecessary cost pressure to the National Health Service, there is a longstanding need for a robust clinical trial to resolve the uncertainty as to whether one treatment is more appropriate than another. Until such data is available, we suggest that provision of stimulated IUI, in centres achieving a satisfactory live birth rate, represents a significant cost-saving to those commissioning fertility services, with lower risks to people treated.

Bilateral tubal and intrauterine pregnancies diagnosed at laparoscopy.

A 32-year-old woman had bilateral tubal and intrauterine pregnancies after hyperovulation with clomiphene citrate and subsequent artificial insemination with husband's semen. Laparoscopic surgery revealed bilateral tubal pregnancies. Salpingectomy was performed on the left tube and linear salpingotomy was performed on the right tube. The postoperative course was uneventful. The patient delivered a healthy girl vaginally at 39 weeks' gestation. Only eight cases with bilateral and intrauterine pregnancy have been reported. The live birth rate of bilateral tubal pregnancy and intrauterine pregnancy is 60% (6/10), which is similar to that of heterotopic pregnancy. Laparoscopic surgery is effective for confirming the diagnosis and treating heterotopic pregnancy.

Influence of follicle rupture and uterine contractions on intrauterine insemination outcome: a new predictive model.

OBJECTIVE: To correlate the detection of follicle rupture and the number of uterine contractions per minute with the outcome of IUI and to build a predictive model for the outcome of IUI including these parameters. DESIGN: Retrospective cohort study. SETTING: Fertility clinic. PATIENT(S): We analyzed data from 610 women who underwent homologous or donor double IUI from 2005 to 2010 and whose data of uterine contractions or follicle rupture were recorded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth rate. RESULT(S): Nine hundred seventy-nine IUI cycles were included. The detection of follicle rupture (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.30-3.01) and the number of uterine contractions per minute (OR, 1.67; 95% CI, 1.02-2.74) assessed after the second insemination procedure of a double IUI were positively correlated with the live-birth rate. A multiple logistic regression model showed that sperm origin, maternal age, follicle count at hCG administration day, follicle rupture, and the number of uterine contractions observed after the second insemination procedure were significantly associated with the live-birth rate. CONCLUSION(S): Follicle rupture and uterine contractions are associated with the success of an IUI cycle. This may open new possibilities to improve the methodology of IUI.

Efficacy and safety of intrauterine insemination and assisted reproductive technology in populations serodiscordant for human immunodeficiency virus: a systematic review and meta-analysis.

OBJECTIVE: To assess procreative outcomes for HIV-positive men and women with seronegative partners. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Twenty-four studies with extractable data for HIV-serodiscordant couples undergoing intrauterine insemination (IUI) or in vitro fertilization (IVF). INTERVENTION(S): None. PRIMARY OUTCOMES: HIV transmission to a seronegative partner and per cycle fecundability; secondary outcomes: analysis of multiple gestation rates, miscarriage rates, and cancellation rates. RESULT(S): For serodiscordant couples, HIV-positive men or women undergoing IUI and IVF treatment had a 17%, 30%, 14%, and 16% per cycle fecundability, respectively. Multiple gestation rates were 10%, 33%, 14%, and 29%, respectively. Miscarriage rates were 19%, 25%, 13%, and 20%, respectively. No HIV transmission was observed in 8,212 IUI and 1,254 IVF cycles, resulting in 95% confidence that the true rate is 4.5 transmissions per 10,000 IUI cycles or less. CONCLUSION(S): In serodiscordant couples, IUI and IVF seem effective and safe based on the literature. Evidence-based practice and social justice suggest that our field should increase access to care for HIV-serodiscordant couples.

[Management of an HTLV-1 infected man in assisted reproductive technology]. / Prise en charge en assistance médicale à la procréation d'un patient infecté par HTLV-1.

Management of people infected by HTLV-1 in assisted reproductive technology (ART) is a rare event. Since HTLV is sexually transmitted, HTLV serodiscordant couples have to systematically use condoms. The sperm processing (centrifugation on density gradient) performed for semen of HIV-infected men was applied. Detection of HTLV-1 provirus DNA was negative before and after sperm processing, allowing ART.

Birth defects after assisted reproductive technologies in China: analysis of 15,405 offspring in seven centers (2004 to 2008).

This first large-scale report of birth defects in 15,405 offspring conceived by assisted reproductive technologies in China found infants born after IVF alone to have a birth defect frequency comparable to that in the general Chinese population; rates were nonsignificantly higher in infants conceived with use of intracytoplasmic sperm injection compared with those conceived after IVF alone.

Stimulated intrauterine insemination: efficient, cost-effective, safe?

A retrospective report of pregnancy and birth rates achieved in 1010 cycles of stimulated intrauterine insemination (SIUI). Over the years there has been an increasing emphasis on safety, particularly towards reducing the number of high order multiple pregnancies. SIUI is a complex form of assisted conception and requires a high level of clinical judgement to maintain an optimal balance between maximising pregnancy and birth rates and minimising complications, of which the most serious is multiple pregnancy. Extrapolating from these results, it is concluded that a well managed SIUI programme that selects patients appropriately, monitors them intensively and has in place effective strategies to manage over-responders safely, should be able to deliver at least a 15% live birth rate per cycle started with only a 5% cycle cancellation rate. Although SIUI birth rates are lower than IVF rates, the much lower cost of SIUI means that this treatment can be more cost-effective than IVF. However SIUI remains more risky than IVF and, despite careful management, high order multiple pregnancy rates will occasionally occur. It is estimated that the rate of unavoidable high order multiple pregnancies (triplets and above) is 4 per 1000 cycles started.

Anaphylactic reaction after artificial insemination.

BACKGROUND: Bovine seroalbumin is known as an allergen for human beings, but reactions to it in an artificial insemination procedure are much rarer. We report a case of anaphylaxis after intrauterine insemination (IUI) in which sensitization to bovine serum albumin (BSA) is demonstrated. OBJECTIVE: Report the allergy evaluation performed in a patient who suffered a severe reaction immediately after an IUI procedure. METHODS: A 33-year-old woman was referred because of an anaphylactic reaction after a second trial of IUI. She developed pruritus, abdominal pain, nausea and vomiting, bronchospasm, and generalized urticaria. She had an atopic medical history of pollen allergy and sensitization to cat epithelium. She had never had trouble with minor surgery and she usually uses latex material. She had never received heterologous sera before. Her husband's semen for the IUI was processed in a standard fluid medium called upgraded INRA B 2 (Laboratoires CCD, Paris, France), which contains amino acids, lipids, vitamins, BSA, penicillin, and streptomycin in addition to inorganic salts. RESULTS: Skin prick tests with the medium and BSA 10 mg/mL were positive. In vitro studies demonstrated an immunoglobulin E binding protein of 60 to 65 kDa and mast cells and basophil activation (CD63 expression) against BSA contained in the medium. Cutaneous and challenge tests with penicillin and streptomycin were negative. CONCLUSIONS: We consider the BSA in the semen culture medium to be the factor which triggered the anaphylactic reaction. This case supports the authors who state that media free from heterologous proteins should be used for human application, especially on atopic patients, to avoid sensitization.

[Etiology and treatment of sterility due to azoospermia]. / Etiologie et traitement de la stérilité due à une azoospermie.

Azoospermia can be classified according to the serum level of FSH into obstructive (OA) or non-obstructive (NOA) azoospermia. It can also be due to a lack of gonadotrophins. In the latter case the administration of FSH and HCG can normalize the sperm production. In the other cases ICSI must be performed. In OA sperm can be retrieved using percutaneous epididymal aspiration or testicular fine needle aspiration in case of failure of vasovasostomy or epididymovasostomy. In NOA or spermatogenic arrest, focal spermatogenesis can be observed in 40 to 50% of cases using repeated testis biopsies, allowing to perform ICSI. Although the risk of malformation in children born after ICSI is not increased there is an increased risk to transmit genetic abnormalities in case of NOA (such as the rate of sex chromosome, or microdeletions of the Y chromosome) and in case of congenital OA (mutations of the cystic fibrosis gene).

[Value of a genetic evaluation before an intracytoplasmic sperm injection procedure]. / Intérêt d'une évaluation génétique lors d'une procédure d'ICSI.

Intracytoplasmic sperm injection (ICSI) still needs to be validated as far as safety is concerned. Results concerning foetal karyotypes currently seem to show an increase in sexual chromosomal abnormalities. In view of the heterogeneity of publications concerning genetic tests, it seems necessary to define a protocol with a limited time span, which will allow the extensive collection of data. The analysis of the results will secondarily allow a common procedure to be established. We propose a protocol limited in time, aiming to evaluate the chromosomal status at birth by a systematic karyotype of umbilical cord blood.