Genetic Counseling for an Infertile Couple With Premature Chromatid Separation (PCS) Syndrome: A Case Report.

We report the first case of successful genetic counseling for an infertile couple with premature chromatid separation (PCS) syndrome. After our careful genetic counseling, the couple decided to continue infertility treatment. As a result, they gave birth to a baby (girl: 2,930 g) by caesarean section in May 2018. To our knowledge, there have not been any published reports regarding genetic counseling for an infertile couple with PCS after PubMed, EMBASE, and Web of Science searches until March 2024.

Endometrial Receptivity Array (ERA) Test in a 32-Year-Old Female With Refractory Infertility: A Case Report.

We report a successful case for the clinical efficacy of the endometrial receptivity array (ERA) test for a 32-year-old female patient with refractory infertility. After our careful treatment, the patient gave birth to a male baby (3390 g) in November 2021. To our knowledge, though the clinical efficacy of the ERA test is controversial until March 2024, we think that the age of the patients, the number of IVF cycles, and the racial differences may have an impact on the clinical efficacy of the ERA test.

Older Women's Reproductive Outcomes May Not Be Improved by the Endometrial Receptivity Analysis Test: A Case Report.

We report a case of a 39-year-old woman with refractory recurrent implantation failure by using endometrial receptivity analysis (ERA) test. According to a recent randomized controlled trial (RCT) study, the ERA test is expected as a helpful tool for the treatment ofinfertile patients with recurrent implantation failures. However, even in the recent RCT study, the efficacy for the ERA test for older patients (more than 38 years old) is still unclear, as the inclusion criterion for the patients in the RCT study was age 37 years or younger. In our research, the patient was 39 years old at the time of the first visit to our clinic. Therefore, the clinical utility of the ERA test may depend on the patient's age. In order to confirm the hypothesis, RCT study for older patients (more than 38 years old) should be conducted. In conclusion, our research showed the limitation of ERA test in patients with recurrent implantation failures. This will save not only our resources but also time before implying any test or investigation for the diagnosis as well management in such patients. Our research will be a good step in the management of such patients.

A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.

RESEARCH QUESTION: Does clinical performance of personalized embryo transfer (PET) guided by endometrial receptivity analysis (ERA) differ from frozen embryo transfer (FET) or fresh embryo transfer in infertile patients undergoing IVF? DESIGN: Multicentre, open-label randomized controlled trial; 458 patients aged 37 years or younger undergoing IVF with blastocyst transfer at first appointment were randomized to PET guided by ERA, FET or fresh embryo transfer in 16 reproductive clinics. RESULTS: Clinical outcomes by intention-to-treat analysis were comparable, but cumulative pregnancy rate was significantly higher in the PET (93.6%) compared with FET (79.7%) (P = 0.0005) and fresh embryo transfer groups (80.7%) (P = 0.0013). Analysis per protocol demonstrates that live birth rates at first embryo transfer were 56.2% in PET versus 42.4% in FET (P = 0.09), and 45.7% in fresh embryo transfer groups (P = 0.17). Cumulative live birth rates after 12 months were 71.2% in PET versus 55.4% in FET (P = 0.04), and 48.9% in fresh embryo transfer (P = 0.003). Pregnancy rates at the first embryo transfer in PET, FET and fresh embryo transfer arms were 72.5% versus 54.3% (P = 0.01) and 58.5% (P = 0.05), respectively. Implantation rates at first embryo transfer were 57.3% versus 43.2% (P = 0.03), and 38.6% (P = 0.004), respectively. Obstetrical outcomes, type of delivery and neonatal outcomes were similar in all groups. CONCLUSIONS: Despite 50% of patients dropping out compared with 30% initially planned, per protocol analysis demonstrates statistically significant improvement in pregnancy, implantation and cumulative live birth rates in PET compared with FET and fresh embryo transfer arms, indicating the potential utility of PET guided by the ERA test at the first appointment.

Comprehensive endometrial immunoglobulin subclass analysis in infertile women suffering from repeated implantation failure with or without chronic endometritis.

PROBLEM: Chronic endometritis (CE) is a local inflammatory condition with unusual plasmacyte infiltration in the endometrial stromal area. CE is frequently found in infertile women with repeated implantation failure (RIF). In this study, we comprehensively investigated the endometrial immunoglobulin (Ig) subclass expression in infertile women suffering from RIF with versus without CE. METHOD OF STUDY: Endometrial biopsy specimens obtained from 28 infertile women with RIF and CE (the RIF-CE group), 23 infertile women with RIF but without CE (the RIF-non-CE group), and 22 proven fertile women undergoing hysterectomy for benign endometrial pathology (the control group) were immunostained for Ig subclass expression. RESULTS: The density of IgM+, IgA1+, IgA2+, IgG1+, and IgG2+ stromal cells were significantly higher in the RIF-CE group than that in the RIF-non-CE and control group. The density of IgG2+ stromal cells was significantly higher than that of any other Ig subclass-positive cells (P<0.045) in the RIF-CE group. In serial section staining, the immunoreactivity for CD138 and Ig subclasses in the endometrial stroma was detectable in adjacent cells of some specimens in the RIF-CE group. CONCLUSIONS: The endometrium of infertile women with RIF-CE was characterized by increase in IgM, IgA, and IgG expression and predominance of IgG2 over other Ig subclasses.

Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

Low follicular fluid tyrosine concentration in infertile women with ovarian hyperstimulation syndrome.

The aim of this study was to compare the branched-chain amino acid (BCAA) and tyrosine concentration in the follicular fluid of infertile women with and without ovarian hyperstimulation syndrome (OHSS) in an in vitro fertilization program combined with controlled ovarian stimulation. Follicular fluid was aspirated during oocyte retrieval from 20 infertile patients who developed moderate-to-severe OHSS and 20 age- and body mass index-matched normoresponders. BCAA and tyrosine concentration were measured using enzymatic methods. The follicular fluid BCAA concentration was similar between the two groups (P=0.55), whereas tyrosine concentration was significantly lower in the OHSS compared to that in the normoresponder group (P=0.027) and the BCAA/tyrosine ratio was significantly higher in the OHSS compared to that in the normoresponder group (P=0.034). These results suggest an association between low follicular fluid tyrosine concentration and OHSS. Dopamine receptor agonists may be used as potential anti-OHSS medicines and tyrosine, as a dopamine precursor, may play a role against the development of OHSS.

Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps.

STUDY QUESTION: Is the endometrial mononuclear cell population in infertile patients altered in subjects with classical endometrial polyps (macropolyps) versus endometrial micropolyps that are hysteroscopically recognized as small uterine cavity protrusions? SUMMARY ANSWER: Macropolypoid endometrium had a low density of pan-leukocytes, pan-T cells and natural killer (NK) cells, whereas micropolypoid endometrium was characterized by high density of B cells and plasmacytes, along with a low density of NK cells. WHAT IS KNOWN ALREADY: Endometrial micropolyps co-exist at a high rate with chronic endometritis, which is an unusual plasmacyte infiltration within the endometrial stromal compartment. STUDY DESIGN: Prospective cross-sectional study. From July 2009 to June 2011, hysteroscopy was performed for infertile women who had been suspected for endometrial macropolyps and who had repeated in vitro fertilization-embryo transfer failure over three or more cycles. Endometrial biopsy samples were obtained from the patients with macropolyps or micropolyps during the proliferative phase. Of 137 patients assessed, 30 were diagnosed with endometrial macropolyps and 34 were diagnosed with endometrial micropolyps. After the exclusion of the cases with heavy uterine bleeding, potential neoplasms, submucosal uterine fibroids, uterine septa, and/or intrauterine adhesion, 23 patients with macropolypoid endometrium; 25 patients with micropolypoid endometrium and 27 patients with non-polypoid endometrium were enrolled in the study. Endometrial macropolyps were surgically removed, whereas chronic endometritis was treated with antibiotics. The patients were followed up until December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The paraformaldehyde-fixed paraffin-embedded endometrial sections were immunostained with monoclonal antibodies against the specific markers of pan-leukocytes (CD45), pan-T cells (CD3), Th cells (CD4), Tc cells (CD8), B cells (CD20), plasmacytes (CD138), NK cells (CD56) and macrophages (CD68). The immunoreactive cells were enumerated in at least 20 non-overlapping stromal areas. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the non-polypoid endometrium, macropolypoid endometrium contained a lower density of pan-leukocytes, pan-T cells and NK cells, whereas micropolypoid endometrium had a higher density of pan-leukocytes and B cells, along with a lower density of NK cells. Following the treatments, 10 patients with macropolypoid endometrium, 11 patients with micropolypoid endometrium and 10 patients with non-polypoid endometrium conceived. LIMITATIONS, REASONS FOR CAUTION: One potential bias is immunohistochemical enumeration for leukocyte density was conducted by one examiner. The limitation of this study is that the results relied on endometrial biopsy specimens, of which immunological conditions may not always represent those in the whole endometrium. WIDER IMPLICATIONS OF THE FINDINGS: There may be some ethnic or racial variances in the composition of the endometrial mononuclear cell subsets of infertile women. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Grand-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (22591840). There were no conflicts of interest to declare.

Diverse functions of uterine proteoglycans in human reproduction (review).

Proteoglycans (PGs) are a group of heavily glycosylated proteins that are present throughout the mammalian body and are involved in a wide variety of biological phenomena, including structural maintenance, tissue remodeling, molecular presentation, cell adhesion and signal transmission. Previous studies have revealed an increasing number of roles for PGs in human reproduction. Several PGs are currently utilized or regarded as biomarkers for the diagnosis of certain pathological uterine conditions associated with infertility and obstetrical complications. The aim of this review was to discuss the involvement of PGs in the human uterus in reproductive biology and pathophysiology.