TAI does not impact on IVF/ICSI outcome in terms of NOR and likelihood of fertilisation, implantation and clinical pregnancy. On the contrary, the presence of thyroid autoantibodies may have a detrimental effect on the course of a pregnancy, determining an increased risk of miscarriage and a decreased chance of live birth. However, given the possible modifying effects of age and serum TSH, further evidence is warranted prior to drawing inferences on causality.

Objectives: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women who achieved MZT and non-MZT pregnancies through IVF. Intervention(s): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. Main Outcome Measure(s): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. Result(s): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the

We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation.

This systematic review of the literature reports on the use and effectiveness of sperm banking programmes for cancer patients. Thirty studies with 11798 patients were included. The aggregated rate of use of cryopreserved semen was 8% (95% CI 8 to 9%). A statistically significant correlation emerged between the mean and median duration of follow-up and the rate of use (R(2) = 0.46; P = 0.03). The rate of patients discarding their frozen sample was reported in 11 studies. The aggregated rate was 16% (95% CI 15 to 17%). The rate of patients who used their frozen semen and achieved parenthood was reported in 19 papers. The aggregated rate was 49% (95% CI 44 to 53%). The rate of patients achieving parenthood with the use of frozen sperm is low and, from an economical perspective, the effectiveness of programmes of sperm banking might therefore be questioned. On the other hand, the low rate of patients discarding their frozen samples and the correlation between rate of use and duration of follow-up suggest that the calculated 8% rate of use may be an under-estimation and that cumulative rate of use may be substantially higher. Specific studies are, however, required to clarify this issue.

The available evidence on the risks of conservative management does not support systematic surgery before IVF in women with small ovarian endometriomas.

The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58–3.00; p < 0.00001; OR 2.03; 95% CI 1.22–3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40–4.16; p = 0.002; OR 3.73; 95% CI 1.13–12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58–3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55–3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.

A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed.

STUDY QUESTION Is there an association between the different endometrial preparation protocols for frozen embryo transfer (FET) and obstetric and perinatal outcomes? SUMMARY ANSWER Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), post-partum hemorrhage (PPH) and cesarean section (CS) when compared with natural FET protocols. WHAT IS KNOWN ALREADY An important and growing source of concern regarding the use of FET on a wide spectrum of women, is represented by its association with obstetric and perinatal complications. However, reasons behind these increased risks are still unknown and understudied. STUDY DESIGN, SIZE, DURATION Systematic review with meta-analysis. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 1 November 2021. Published randomized controlled trials, cohort and case control studies were all eligible for inclusion. The risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. The quality of evidence was also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies were included only if investigators reported obstetric and/or perinatal outcomes for at least two of the following endometrial preparation protocols: programmed FET cycle (PC-FET) (i.e. treatment with hormone replacement therapy (HRT)); total natural FET cycle (tNC-FET); modified natural FET cycle (mNC-FET); stimulated FET cycle (SC-FET). MAIN RESULTS AND THE ROLE OF CHANCE Pooled results showed a higher risk of HDP (12 studies, odds ratio (OR) 1.90; 95% CI 1.64–2.20; P &lt; 0.00001; I2 = 50%) (very low quality), pregnancy-induced hypertension (5 studies, OR 1.46; 95% CI 1.03–2.07; P = 0.03; I2 = 0%) (very low quality), PE (8 studies, OR 2.11; 95% CI 1.87–2.39; P &lt; 0.00001; I2 = 29%) (low quality), placenta previa (10 studies, OR 1.27; 95% CI 1.05–1.54; P = 0.01; I2 = 8%) (very low quality), PPH (6 studies, OR 2.53; 95% CI 2.19–2.93; P &lt; 0.00001; I2 = 0%) (low quality), CS (12 studies, OR 1.62; 95% CI 1.53–1.71; P &lt; 0.00001; I2 = 48%) (very low quality), preterm birth (15 studies, OR 1.19; 95% CI 1.09–1.29; P &lt; 0.0001; I2 = 47%) (very low quality), very preterm birth (7 studies, OR 1.63; 95% CI 1.23–2.15; P = 0.0006; I2 = 21%) (very low quality), placenta accreta (2 studies, OR 6.29; 95% CI 2.75–14.40; P &lt; 0.0001; I2 = 0%) (very low quality), preterm premature rupture of membranes (3 studies, OR 1.84; 95% CI 0.82–4.11; P = 0.14; I2 = 61%) (very low quality), post-term birth (OR 1.90; 95% CI 1.25–2.90; P = 0.003; I2 = 73%) (very low quality), macrosomia (10 studies, OR 1.18; 95% CI 1.05–1.32; P = 0.007; I2 = 45%) (very low quality) and large for gestational age (LGA) (14 studies, OR 1.08; 95% CI 1.01–1.16; P = 0.02; I2 = 50%) (very low quality), in PC-FET pregnancies when compared with NC (tNC + mNC)-FET pregnancies. However, after pooling of ORs adjusted for the possible confounding variables, the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP, PE, PPH (low quality) and CS (very low quality). LIMITATIONS, REASONS FOR CAUTION The principal limitation concerns the heterogeneity across studies in: (i) timing and dosage of HRT; (ii) embryo stage at transfer; and (iii) inclusion of preimplantation genetic testing cycles. To address it, we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor. WIDER IMPLICATIONS OF THE FINDINGS Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes. However, because of the methodological weaknesses, recommendations for clinical practice cannot be made. Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an ‘a priori’ high-risk profile for obstetric and perinatal complications. STUDY FUNDING/COMPETING INTEREST(S) None. REGISTRATION NUMBER CRD42021249927.