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Résumé Les examens biologiques conventionnels d’exploration du sperme (spermogramme–spermocytogramme) sont parmi les examens de première intention dans le bilan diagnostique de l’infertilité d’un couple. En cas de prise en charge thérapeutique par une technique d’assistance médicale à la procréation, ils devront être complétés par un test de sélection spermatique appelé test de migration-survie. Usuellement, tous ces examens sont réalisés via des techniques manuelles qui, malgré une méthodologie codifiée, sont soumises à des sources de variabilité nombreuses, imposant un suivi très régulier du maintien des compétences techniques au sein du laboratoire via notamment des contrôles de qualité pluri-annuels. Le biologiste doit donc être conscient du caractère subjectif de certains examens de spermiologie, savoir en limiter les effets. Pour le spermocytogramme, il doit savoir argumenter le référentiel choisi, connaître leurs normes afférentes et être conscient de l’absence de bénéfice démontré du détail des différentes anomalies morphologiques spermatiques. Dans ce contexte, le développement d’approches automatisées pour la spermiologie standard est louable et doit être favorisé, bien que ces approches présentent certaines limites et, que du fait de leurs coûts, elles imposent un certain volume d’activité. Conventional semen parameters (spermogram, sperm morphology) are among first line diagnostic tests to perform when facing an infertile couple. Furthermore, if a therapeutic intervention is needed, they must be completed by a sperm preparation technic allowing to witness which assisted reproductive option is possible from a male point of view. All analysis of semen parameters are usually performed using manual technics whose methodology is highly codified but that are known to be submitted to several sources of variability, notably the operator, imposing a regular assessment of technical skills using pluri-annual quality controls. The biologist must be aware of the subjectivity of numerous semen parameters and must know how to cope with to limit its effects. Regarding, sperm morphology, he must know the reference values of the classification he used and can argument on the reasons to choose it, be aware of the lack of clinical evidence to perform a detailed analysis of every possible sperm abnormalities. In this context, the implementation of automatized approaches of standard semen evaluation is probably a positive point, although they also have constraints and limitations, among which their cost, needing a minimal volume of activity to be considered. [ABSTRACT FROM AUTHOR]

Objective: To evaluate rates and reasons for treatment discontinuation in couples with male factor infertility and who failed to conceive. Design: Retrospective study. Setting: Male Sterility Center, University Hospital. Patient(s): A total of 407 couples consulting for male factor infertility and who discontinued treatment without conceiving. Intervention(s): None. Main Outcome Measure(s): Treatment, reasons for dropout, and reproductive outcomes after discontinuation. Result(s): Of the 407 patients, 218 (54%) had had fertility treatment (medical or surgical), and 189 (46%) underwent assisted reproductive techniques (ART) (intrauterine insemination [IUI], in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI]). The main reasons for dropout were painfulness of treatment (15% for patients with non-ART treatment vs. 32% for patients who had undergone ART), its ineffectiveness (12% vs. 26%), and separation of the couple (18% vs. 7%). Of the 407 patients, 27% consulted in another fertility center, 8% succeeded in having a child by ART with male partner sperm, 1% by ART with donor sperm, and 11% through adoption. Conclusion(s): About half of the couples consulting for male factor infertility discontinued fertility treatment, and of those who discontinued only a fifth finally succeeded in having a child. Although support is available to couples during fertility care, ART is a physical and psychological burden. [ABSTRACT FROM AUTHOR]

Since the development of the motile sperm organellar morphology examination (MSOME) in 2001 for observing the cephalic vacuoles at high magnification, no study as yet assessed the effect of cryopreservation on these vacuoles, although sperm freezing-thawing procedures are known to affect sperm quality. Examination of the vacuoles before and after freezing-thawing would indicate whether the same normality criteria can be applied for frozen as for fresh spermatozoa when performing intracytoplasmic morphologically selected sperm injection. In 27 sperm samples from fertile men, analysis of conventional sperm parameters (motility, vitality, percentage of normal forms) and a morphological analysis at high magnification (x6000) using image analysis software was performed before freezing and after thawing. Whereas there were expected decreases in motility (P < 0.0001), vitality (P < 0.001) and percentage of normal forms (P < 0.05) after cryopreservation, there was no evidence for any difference in any vacuolar criteria (relative vacuole area, total vacuole area, vacuole area in the anterior, median and basal parts of the head, percentage of spermatozoa with a vacuole area ≤6.5% and percentage of spermatozoa with a vacuole area >13%). Freezing-thawing procedures have no effect on human sperm vacuoles. [ABSTRACT FROM AUTHOR]

Research question: Although the impact of cystic fibrosis on male fertility is well known, very few studies have investigated its effect on female fertility. This study aimed to evaluate the fertility status of women with cystic fibrosis. Design: A questionnaire was sent to 220 women with cystic fibrosis. The questions concerned their desire to become a parent, achievement or not of a pregnancy, the time to become pregnant, the means of achieving pregnancy (spontaneously or with medical assistance) and the outcome of the pregnancy. Ninety-eight patients responded to the questionnaire. Results: Of the 46 women who sought pregnancy, 25 (54%) had at least one live birth without treatment, while 11 (24%) required infertility treatment to obtain a live birth and 10 (22%) had no delivery. The mean time-to-pregnancy was 12 months (1–180). The reasons for preferring not to become pregnant were mainly fear of the interaction between cystic fibrosis and pregnancy and of the transmission of cystic fibrosis to children. Conclusions: Fertility seems to be slightly impaired in women with cystic fibrosis, because 37% of them failed to become pregnant without medical assistance. Because the outcome of pregnancies appears normal, patients should be informed about the possibility of becoming mothers and be made aware of the risk of unwanted pregnancies. [ABSTRACT FROM AUTHOR]

What is the association between blood progesterone level alone, progesterone to mature oocytes index (PMOI) and IVF outcomes? Clinical data from 960 couples undergoing their first fresh embryo transfer after an intracytoplasmic sperm injection attempt carried out between September 2012 and July 2017 were analysed. All patients underwent ovarian stimulation combining recombinant FSH and gonadotrophin releasing hormone antagonist. Progesterone was measured on the day on which ovulation was triggered. The PMOI was divided into four groups based on 25th, 50th and 75th percentiles, and live birth and implantation rates were compared between the groups. A negative association was found between PMOI levels, live birth and implantation rates. When adjusting for age, ovarian stimulation index (OSI) and number of embryos transferred, the PMOI remained negatively correlated to live birth rate (LBR) (OR = 0.147 [0.031 to 0.701]; P = 0.0161), whereas total blood progesterone was no longer evident. Moreover, the LBR (18.5% versus 28.4%; P < 0.01) and implantation rate (12.4% versus 21.0%; P < 0.01) were significantly decreased only when PMOI was 0.167 ng/ml or greater, irrespective of progesterone concentration (< or ≥1.08 ng/ml). The opposite was not true, however. Similar PMOIs were recorded in the same patient from one attempt to the next, and were partially linked to basal FSH, anti-Müllerian hormone, antral follicle count and OSI. PMOI seems to be more predictive than total progesterone level of IVF outcome and reflects the ability of embryos to develop as it is linked to the implantation rate. [ABSTRACT FROM AUTHOR]

Abstract Research question Anti-sperm antibodies (ASA) have been shown to reduce male fertility but consensus about the precise situations in which tests should be carried out are lacking. In infertility investigations, should the mixed antiglobulin reaction (MAR) test be a first-line test? Should it be carried out systematically before assisted reproductive technology (ART)? What are the risk factors for ASA? Design All infertile patients (n = 1364) were tested with SpermMar (modified MAR test) between July 2013 and June 2017. Intra-patient variability of the MAR test was also assesed by comparing two tests within the same year in selected patients (n = 101). Results The main factor that influenced the percentage of ASA was the presence or absence of sperm agglutination. In the presence of agglutinations, 27 out of 72 (37.5%) patients were positive for ASA compared with 33 out of 1292 (2.6%) in the absence of agglutinations (P < 0.0001). When one risk factor was present (spontaneous sperm agglutination, history of scrotal trauma or inguinal surgery), 33 out of 179 (18.44%) tests were positive for ASA (≥50% coated spermatozoa), whereas only 27 out of 1242 (2.2%) were positive when no risk factor was present (P < 0.0001). Conclusions ASA detection should not be systematically recommended in investigations of fertility status and before ART but reserved for when sperm agglutination is found during conventional sperm examination, or if the patient has a history of scrotal trauma or has undergone inguinal surgery. [ABSTRACT FROM AUTHOR]

This study aimed to integrate clinical and biological parameters in a score able to predict ovarian response to stimulation for IVF in gonadotrophin-releasing hormone (GnRH) antagonist protocols. A progressive discriminant analysis to establish a score including the main clinical and biological parameters predicting ovarian response was performed by retrospectively analysing data from the first ovarian stimulation cycle of 494 patients. The score was validated in a prospectively enrolled, independent set of 257 patients undergoing their first ovarian stimulation cycle. All ovarian stimulations were performed using a combination of GnRH antagonist and recombinant FSH. Ovarian response was assessed through ovarian sensitivity index (OSI). Parameters from the patients' database were classified according to correlation with OSI: the progressive discriminant analysis resulted in the following calculation: score = 0.192 – (0.004 × FSH (IU/l)) + (0.012 × LH:FSH ratio) + (0.002 × AMH (ng/ml)) – (0.002 × BMI (kg/m 2 )) + (0.001 × AFC) – (0.002 × age (years)). This score was significantly correlated with OSI in the retrospective ( r = 0.599; P < 0.0001) and prospective ( r = 0.584; P < 0.0001) studies. In conclusion, the score including clinical and biological parameters could explain 60% of the variance in ovarian response to stimulation. [ABSTRACT FROM AUTHOR]

A total of 101 patients with one normal tube were compared with 117 patients with two normal tubes to assess the effect of unilateral tubal abnormalities on the results of intrauterine inseminations. The clinical pregnancy and live birth rates seemed to reduce by one-half in almost all types of abnormality, suggesting that these patients should be preferentially treated with IVF. [ABSTRACT FROM AUTHOR]

Objective: To developed a prognostic score to predict ongoing implantation rate according to clinical and biological parameters and to choose the number of embryos to be transferred in patients undergoing IVF/ICSI.Study Design: The transfer score was established using multivariate analysis of biological and clinical parameters in 3211 fresh embryo transfers in a retrospective study. Then we validated the score in 694 fresh embryo transfers in a prospective study. We assessed ongoing implantation rates, ongoing pregnancy rates, multiple pregnancy rates and live birth rate.Results: Among the different variables tested, 4 were identified that influenced the implantation rate: female age, the ratio of retrieved oocytes/mean daily dose of injected FSH, attempt rank and the morphology of the embryo cohort. Prospective application of this score resulted in significantly lower number of transferred embryos (1.8 vs 2.0 P<0.001) and lower twins rates (9.7% vs 17.3%, P<0.001) without decreasing live birth rates.Conclusion: Although the risks of multiple pregnancies should not be ignored, it appears excessive to impose the limit of 2 embryos for transfer particularly in situations with a poor prognosis. We sought to provide a personalized prognosis by using clinical and embryo data in order to choose the number of embryo(s) for transfer with a moderate multiple pregnancy rate of less than 11%. [ABSTRACT FROM AUTHOR]

Objective: To assess the influence of air quality on the results of IVF.Study Design: We performed a retrospective study on 292 patients who have undergone an IVF attempt from April 2012 to December 2015 in our French university hospital. Patients were included in the study if data on the air quality at home and at work were available and if they haven't been gone for more than 4days in a month. Data were recorded during the 3 months before oocyte collection and 1 month after embryo transfer. Air quality measurements were obtained from the Observatoire Régional de l'Air en Midi-Pyrénées (ORAMIP) and concerned the levels of nitrogen dioxide (NO2), ozone (O3), particulate matter PM10 and SO2 measured every day.Results: Acute exposures to high levels NO2 or PM10 were associated with lower results of IVF (ovarian response to stimulation, number of top embryos) while these parameters were enhanced when patients were exposed to high levels of O3 during the first 2 months of folliculogenesis. These effects were found even for a short exposure (1day).Conclusions: Air quality has an impact on global health and also on the reproductive function and public and authorities must be aware of environmental protection. [ABSTRACT FROM AUTHOR]

Objective: To determine the best practices of intrauterine insemination with the partner's fresh sperm.Design: Prospective multicenter observational study.Setting: Assisted reproduction technology (ART) centers.Patient(s): Seven hundred and seven patients entering the program, regardless of age or cause of infertility.Intervention(s): Intrauterine insemination by standard procedures.Main Outcome Measure(s): Effect of patient characteristics (duration of infertility, indications, age, parity, body mass index, semen parameters) as well as IUI parameters on delivery rates per couple or per attempt.Result(s): The overall live birth rate was 11.4% per cycle, varying from 8.4% to 17.6% between centers. The main differences in practice that had a statistically significant impact on the delivery rate were the use of gonadotropin-releasing hormone (GnRH) antagonists (15.2% with versus 9.4% without) and the number of mature recruited follicles (9.4% for one versus 15.2% for two).Conclusion(s): Our results indicate that the use of GnRH antagonists has a positive effect on the delivery rate, especially in the multifollicular stimulations that are required when women are older than 27 years. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the percentage of couples achieving parenthood and the rate of separation 6 years after their first consultation for infertility.Study Design: Epidemiological study in the reproductive medicine department of a French university hospital. All first consulting couples (FCC) who had their first infertility consultation in the department in 2007 were contacted by phone and asked to respond to a questionnaire concerning their infertility treatments, parenthood and marital status 6 years after their first consultation.Results: Of the 685 FCC, 94 could not be contacted, 34 refused to respond and 557 (86%) answered the questionnaire. Of 557 FCC who have responded, 361 (65%) have achieved parenthood: 166 (46%) after treatment, 98 (27%) after spontaneous conception, 38 (11%) after both spontaneous and treatment-induced conception and 59 (16%) through adoption. Parenthood was not influenced either by the causes or duration of infertility. Separation occurred in 53 (9.5%) of FCC, mainly in those without any children (28% vs 4% in FCC with at least one child; P<.0001).Conclusion: Six years after their primary consultation, 25% of couples remained childless and 28% of them were separated. [ABSTRACT FROM AUTHOR]

Objective To compare the continuation of in vitro fertilization (IVF) with the conversion to intrauterine insemination (IUI) in cases of suboptimal ovarian response in Bologna-criteria poor responders. Design Retrospective and multicenter comparative study. Setting Three academic fertility centers and a fertility private clinic. Patient(s) Analysis of 7,176 initiated IVF cycles from January 2010 to January 2013. The 461 cycles with poor ovarian response (fewer than three follicles ≥16 mm at hCG trigger) in patients with poor response according to the Bologna criteria were included. Intervention(s) Decision to pursue IVF (n = 184), convert to IUI (n = 141), or cancel cycle (n = 136) when only one or two follicles were recruited. Main Outcome Measure(s) Live birth, ultrasound pregnancy, and early pregnancy rates were compared depending on whether they resulted from IVF or IUI and were stratified according to patient age and the number of mature follicles at trigger. Result(s) Live birth rates were significantly higher for IVF patients compared with IUI conversion when two follicles were present (11.6% IVF vs. 1.6% IUI), especially for patients <40 years of age (13.1% IVF vs. 2% in IUI). In case of a monofollicular recruitment, the pregnancy outcomes were similar. Conclusion(s) A therapeutic strategy could therefore be to pursue IVF for women demonstrating two follicles and to convert to IUI for cycles with only one follicle if the sperm and tubal parameters are favorable. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of a computerized decision support system for ovarian stimulation with gonadotropins.Design: Retrospective and prospective randomized studies.Setting: Private and university teaching hospital.Patient(s): Women undergoing ovarian stimulation to treat infertility.Main Outcome Measure(s): Pregnancy rate.Result(s): In the retrospective study, computer-generated decisions were compared with clinicians' decisions in 118 stimulated cycles in 53 patients. In 90% of cases, the choice of FSH regimens and adjustments to dosages were identical. In the prospective study, the computer-generated decisions achieved a pregnancy rate per cycle of 18% (15 of 82 cycles), compared with 16% (13 of 82 cycles) achieved by clinicians.Conclusion(s): A computerized decision making system was as effective as skilled clinicians in achieving pregnancy by using ovarian stimulation with FSH. [ABSTRACT FROM AUTHOR]

Objective: To investigate current practices for sperm morphology assessment.Design: E-mail survey questionnaire.Setting: Diagnostic and clinical institutions/laboratories.Patient(s): French biologists and clinicians (n = 225).Intervention(s): None.Main Outcome Measure(s): Answers to 24 questions.Result(s): The survey shows that even now in France there is great inconsistency in the use of sperm morphology assessments. For example, the survey revealed that no fewer than six different staining techniques were in use. Automatic reading is hardly used (used by 2.5% of the biologists replying to the survey). More than 33.6% of biologists use a threshold of normal forms unsuited to their classification, and 20% do not perform any internal quality control in this area. Prescribing doctors seldom trust the tests, likely due to their lack of analytic reliability. Among the biologists surveyed 26% said the percentage of normal forms is either unreliable or not very reliable in analytic terms, and 24% of clinicians stated that it has little clinical relevance.Conclusion(s): The survey reveals a marked lack of uniformity in French laboratories for performing sperm morphology assessment and in the use of the results by physicians. Regular quality control procedures and well-trained personnel, up to date with their training and conversant with the latest techniques as well as harmonized practices, are clearly indispensable. It is time for a consensus on the practice and interpretation of this particular test. [ABSTRACT FROM AUTHOR]