OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples.
METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts.
RESULTS: The fertility work-up is recommended to be prescribed according to the woman\'s age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple\'s initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery.
CONCLUSIONS: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

OBJECTIVE: Is pregnancy success rate after a concise infertility work-up the same as pregnancy success rate after the traditional extensive infertility work-up?
CONCLUSIONS: The ongoing pregnancy rate within a follow-up of 1 year after a concise infertility work-up is significantly lower than the pregnancy success rate after the traditional and extensive infertility work-up.
BACKGROUND: Based on cost-effectiveness studies, which have mainly focused on diagnosis, infertility work-up has become less comprehensive. Many centres have even adopted a one-stop approach to their infertility work-up.
UNASSIGNED: We performed a historically controlled cohort study. In 2012 and 2013 all new infertile couples (n = 795) underwent an extensive infertility work-up (group A). In 2014 and 2015, all new infertile couples (n = 752) underwent a concise infertility work-up (group B). The follow-up period was 1 year for both groups. Complete follow-up was available for 99.0% of couples in group A and 97.5% in group B.
METHODS: The extensive infertility work-up consisted of history taking, a gynaecological ultrasound scan, semen analysis, ultrasonographic cycle monitoring, a timed postcoital test, a timed progesterone and chlamydia antibody titre. A hysterosalpingography (HSG) was advised routinely. The concise infertility work-up was mainly based on history taking, a gynaecological ultrasound scan and semen analysis. A HSG was only performed if tubal pathology was suspected or before the start of IUI. Laparoscopy and hormonal tests were only performed if indicated. Couples were treated according to the diagnosis with either expectant management (if the Hunault prognostic score was >30%), ovulation induction (in case of ovulation disorders), IUI in natural cycles (in case of cervical factor), IUI in stimulated cycles (if the Hunault prognostic score was <30%) or IVF/ICSI (in case of tubal factor, advanced female age, severe male factor and if other treatments remained unsuccessful). The primary outcomes were time to pregnancy and the ongoing pregnancy rates in both groups. The secondary outcomes were the number of investigations, the distribution of diagnoses made, the first treatment (started) after infertility work-up and the mode of conception.
RESULTS: The descriptive data, such as age, duration of infertility, type of infertility and lifestyle habits, in both groups were comparable. In group A, more than twice the number of infertility investigations were performed, compared to group B. An HSG was made less frequently in group B (33% versus 42%) and at a later stage. A Kaplan-Meier curve shows a shorter time to pregnancy in group A. Also, a significantly higher overall ongoing pregnancy rate within a follow-up of 1 year was found in group A (58.7% versus 46.8%, respectively, P < 0.001). In group A, more couples conceived during the infertility work-up (14.7% versus 6.5%, respectively, P < 0.05). The diagnosis cervical infertility could only be made in group A (9.3%). The diagnosis unexplained infertility differed between groups, at 23.5% in group A and 32.2% in group B (P < 0.001).
CONCLUSIONS: This was a historically controlled cohort study; introduction of bias cannot be ruled out. The follow-up rate was similar in the two groups and therefore could not explain the differences in pregnancy rate.
CONCLUSIONS: Re-introduction of an extensive infertility work-up should be considered as it may lead to higher ongoing pregnancy rates within a year. The therapeutic effects of HSG and timing of intercourse may improve the fertility chance. This finding should be verified in a randomized controlled trial.
BACKGROUND: No funding was obtained for this study. No conflicts of interest were declared.
BACKGROUND: N/A.

What is the relationship between the degree of sperm autoimmunisation, as assessed by IgG-mixed antiglobulin reaction (MAR) test, and natural and intrauterine insemination (IUI)-assisted live births?
Compared with a lower degree of positivity (50-99%), a 100%-positive MAR test was associated with a much lower occurrence of natural live births in infertile couples, who could be successfully treated with IUI, as first-line treatment.
The World Health Organization (WHO) has recommended screening for antisperm antibodies, through either the IgG-MAR test or an immunobead-binding test, as an integral part of semen analysis, with 50% antibody-coated motile spermatozoa considered to be the clinically relevant threshold. However, the predictive value of the degree of positivity of the MAR test above such a cut-off on the occurrence of natural pregnancies remains largely undetermined. Furthermore, the effectiveness of IUI in cases of strong sperm autoimmunisation is not yet well-established.
This was a retrospective cohort study on 108 men with a ≥50%-positive MAR test, where the couple had attended a university/hospital andrology/infertility clinic for the management of infertility from March 1994 to September 2017.
The IgG-MAR test was carried out as an integral part of semen analysis. The patients were divided into two groups: 100% and 50%-99%-positive MAR test. The post-coital test (PCT) was performed in all the couples, and IUI was offered as the first-line treatment. Laboratory and other clinical data were retrieved from a computerised database. Data on subsequent pregnancies were obtained by contacting patients over the telephone.
A total of 84 men (77.8%) were successfully contacted by telephone, and they agreed to participate. Of these, 44 men belonged to the group with a 100%-positive MAR test, while 40 showed lower MAR test positivity. The couples with a 100%-positive MAR test showed a natural live birth rate per couple (LBR) that was considerably lower than that observed with a lower degree of positivity (4.5% vs. 30.0%; P = 0.00001). Among the clinical variables, a significant difference between the two groups was observed only for the PCT outcome, which was poor in the 100%-positive MAR test group. Better PCT outcomes (categorised as negative, subnormal and good) were positively associated with the occurrence of natural live births (6.3, 21.7 and 46.2%, respectively; P = 0.0005 for trend), for which the sole independent negative predictor was the degree of sperm autoimmunisation. IUI was performed as the first-line treatment in 38 out of 44 couples with a 100%-positive MAR test, yielding 14 live births (36.8%). In couples with lower MAR test positivity, the LBR after IUI (26.9%) was similar to the natural LBR in this group (30.0%).
Given the retrospective nature of the study, we cannot exclude uncontrolled variables that may have affected natural pregnancies during the follow up or a selection bias from the comparison of natural live births with those after IUI.
The routine use of the IgG-MAR test in the basic fertility workup is justified as it influences decision making. A 100%-positive IgG-MAR test can represent the sole cause of a couple\'s infertility, which could be successfully treated with IUI. On the other hand, a lower degree of positivity may only represent a contributing factor to a couple\'s infertility, and so the decision to treat or wait also depends on the evaluation of conventional prognostic factors including the PCT outcome.
This study was supported by PRIN 2017, Ministero dell\'Università e della Ricerca Scientifica (MIUR), Italy. On behalf of all authors, the corresponding author states that there is no conflict of interest.
N/A.

OBJECTIVE: Many fertility clinics have decided to abolish the post-coital test. Yet, it is a significant factor in prognostic models that predict the spontaneous pregnancy rate within one year. The aim of this study was to evaluate (1) the long-term outcome of infertile couples with a positive or a negative post-coital test during their fertility work-up and (2) the contribution of the different modes of conception.
METHODS: Retrospective cohort study.
METHODS: Three fertility clinics in the Netherlands, of which two are secondary care training hospitals and is a one tertiary care academic training hospital.
METHODS: 2476 newly referred infertile couples, where a post-coital test was performed in 1624 couples.
METHODS: After basic fertility work-up, couples were treated according to the national treatment protocols.
METHODS: Spontaneous and overall ongoing pregnancy rate.
RESULTS: The spontaneous and overall ongoing pregnancy rates after three years were 37.7 and 77.5% after a positive post-coital test compared with 26.9 and 68.8% after a negative test (p < 0.001). Even in couples with severe male factor infertility (total motile sperm count <3) (p = 0.005) and mild male factor infertility (total motile sperm count 3-20) (p < 0.001), there was a significantly higher spontaneous ongoing pregnancy rate, justifying expectant management.
CONCLUSIONS: After a follow-up of three years a positive post-coital test is still associated with a higher spontaneous and a higher overall ongoing pregnancy rate, even in couples with severe male factor infertility.