About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents’ will. The placenta pathologically suggested hemoperfusion problems. Her and her husband’s chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient’s immunological aberration.

Study question In the management of male infertility, we investigated whether urological consultation could improve the live birth rate, and who should visit urologists in the setting of IVF clinic. Summary answer Urologic consultation resulted in improvement of semen quality and live birth rate with more IVF use in those with adverse semen parameters. What is known already Male factor infertility exists in about a half of infertility couples. This accounts for about 8% in male reproductive age. Therefore, ideally every male partner of infertility couples attempting conception should have a urological evaluation. However, it is not very easy to access urologists who specialized in reproductive medicine in Japan because we have very few of such urologists. One the other hand, a certain number of couples are wasting their time during IVF failure without urological evaluation. Study design, size, duration This is a single-institution retrospective study. We enrolled male partners of infertility couples who visited Kameda IVF clinic Makuhari, Chiba, Japan, between May 2016 and December 2020 and followed at least one year. Live birth rate and the frequency of IVF use were investigated according to semen quality and urological consultation status. Chi-square tests and T tests were used to compare the results between groups. Participants/materials, setting, methods Among 2225 couples who visited Kameda IVF clinic Makuhari, 803 male partners (Group A, 36.0%) were evaluated by urologists who were specialized in male reproductive medicine. Remaining 1422 patients did not (Group B, 64.0%). Lifestyle evaluation, physical examination, semen analyses, scrotal ultrasonography, blood test including sexual hormones and zinc concentration were performed in Group A. Semen analyses and lifestyle evaluation were performed in Group B. Urological treatments were done according to factors of male infertility. Main results and the role of chance Semen quality was worse in Group A as compared to Group B (sperm motility, 28.5±16.9% vs. 46.0±17.0%; total sperm count, 105±108 million/mL vs. 176±155; total motile sperm count, 34±49 vs.87±98; mean±S.D.; p = 0.0001, 0.0001, 0.0001, A vs. B, respectively). After urologic consultation and managements, sperm motility was improved to 34±18% (p = 0.001). Live birth rate in groups A and B were similar (56.0% vs. 57.2%), however couples who obtained a child in Group A used IVF more often than those in Group B (70% vs. 49.9%, p < 0.001). Among those with adverse semen quality (total motile sperm count less than 15.6 million/mL, n = 472), 350 visited urologists (Group 1, 74.2%) and remaining 122 did not (Group 2, 25.8%). Live birth rate in Group 1 was significantly better than in Group 2 (65.3% vs. 54.1%, p = 0.0359). Use of IVF was significantly more frequent in Group 1 than Group 2 (79.3% vs. 63.6%, p = 0.0359) among who obtained a child. In those with better semen quality (motile sperm count >50 million, n = 900), 119 visited urologist (31.1%, Group 3) and 781 did not (Group 4). Live birth rate and the use of IVF were not different between Groups 3 and 4 (51.1% vs.60.9%; 50.4% vs. 62.9%). Limitations, reasons for caution This study is a single-institution, retrospective study in the setting of IVF clinic. There may be a selection bias since men first visit gynecologists. These could affect the study results. Wider implications of the findings In the setting of IVF clinic, urologic consultation resulted in improved semen quality and better live birth rate with the use of IVF, especially in those who have adverse semen parameters. The results of this study encourage patients to see urologists and physicians to introduce urologist to patients. Trial registration number not applicable

Background: Recurrent miscarriage (RM), defined as three or more miscarriages, is estimated to occur in 1–3% of couples trying to conceive. Although several established causes of RM have been reported, the causes for half of all cases remain unexplained. Occasional antiphospholipid antibody (aPL)-positivity not diagnosed as antiphospholipid syndrome (APS) could be a risk factor for unexplained RM. However, no established treatment has been documented for patients with occasional aPL-positivity.Case presentation: This patient with unexplained infertility underwent in vitro fertilization (IVF) and experienced three continuous miscarriages, including chemical pregnancy. The general screening for RM detected only aPL-IgG. However, the negative result obtained by the retest 12 weeks later suggested the case as an unexplained RM with occasional aPL-positivity not diagnosed with APS. Low-dose aspirin (LDA; enteric-coated aspirin tablet, 100 mg once daily) as an anticoagulant was administered on the day of embryo transfer (ET) and continued until a successful clinical pregnancy was determined. Although implantation was achieved with this intervention, a successful clinical pregnancy could not be achieved. Thereafter, low-molecular-weight heparin (LMWH; 10,000 IU every 12 h) and LDA (enteric-coated aspirin tablet, 100 mg once daily) were administered everyday starting on the day of ET and continued till 14 and 28 weeks of gestation, respectively. On day 16 post-ET, the serum β-human chorionic gonadotropin concentration was elevated to 2562.0 IU/L, and an ultrasound confirmed the pregnancy. The patient successfully completed the course of pregnancy and delivered a viable female neonate (3010 g) at 40 weeks and 3 days of gestation.Conclusions: This case demonstrated that the combination therapy of LMWH and LDA led to a successful pregnancy and live birth in a patient with occasional aPL-positivity but not APS. However, further clinical trials are required to confirm the efficacy of the combined therapy of LMWH and LDA in patients with unexplained RM associated with occasional aPL-positivity.