Case-based survey: The impact of breast-cancer treatment on fertility in Japan.

AIM: To assess the impact of breast-cancer treatment on fertility. METHODS: We conducted a retrospective, case-based survey of treatments administered for infertility and pregnancy outcomes after patients underwent treatment for breast cancer. Surveys were distributed to breast oncology facilities and reproductive endocrinology and infertility (REI) facilities. RESULTS: As high as 60% of the pregnancies in women under the age of 35 years occurred spontaneously. Additionally, the fertility rates decreased as age increased (under 35 years of age: 40%, 35-39 years of age: 21%, 40-44 years of age: 10%, respectively). In women who became pregnant after treatment for breast cancer, conception was achieved within 1 to 3 years after beginning to try for pregnancy. CONCLUSIONS: After treatment for breast cancer, women can expect spontaneous pregnancy, especially if they are under 35 years of age. It is important for patients 35 years of age and older to commence assisted reproductive technology in a timely manner when pursuing fertility after treatment for breast cancer.

Contribution of senescence in human endometrial stromal cells during proliferative phase to embryo receptivity†.

Successful assisted reproductive technology pregnancy depends on the viability of embryos and endometrial receptivity. However, the literature has neglected effects of the endometrial environment during the proliferative phase on implantation success or failure. Human endometrial stromal cells (hESCs) were isolated from endometrial tissues sampled at oocyte retrieval during the proliferative phase from women undergoing infertility treatment. Primary hESC cultures were used to investigate the relationship between stemness and senescence induction in this population and embryo receptivity. Patients were classified as receptive or non-receptive based on their pregnancy diagnosis after embryo transfer. Biomarkers of cellular senescence and somatic stem cells were compared between each sample. hESCs from non-receptive patients exhibited significantly higher (P < 0.01) proportions of senescent cells, mRNA expressions of CDKN2A and CDKN1A transcripts (P < 0.01), and expressions of genes encoding the senescence-associated secretory phenotype (P < 0.05). hESCs from receptive patients had significantly higher (P < 0.01) mRNA expressions of ABCG2 and ALDH1A1 transcripts. Our findings suggest that stemness is inversely associated with senescence induction in hESCs and, by extension, that implantation failure in infertility treatment may be attributable to a combination of senescence promotion and disruption of this maintenance function in this population during the proliferative phase of the menstrual cycle. This is a promising step towards potentially improving the embryo receptivity of endometrium. The specific mechanism by which implantation failure is prefigured by a loss of stemness among endometrial stem cells, and cellular senescence induction among hESCs, should be elucidated in detail in the future.

Meiotic spindle size is a strong indicator of human oocyte quality.

PURPOSE: To investigate the relationship between the meiotic spindle size in human metaphase II oocytes and embryo developmental potential after intracytoplasmic sperm injection (ICSI). METHODS: Analyzed were 1302 oocytes with a visible meiotic spindle from 281 patients aged under 40 years undergoing ICSI cycles. The meiotic spindle was imaged by using PolScope before ICSI. The oocytes were classified into three groups, according to spindle size: group A (<90 µm2), group B (90-120 µm2), and group C (>120 µm2). RESULTS: Overall, 389 (29.9%) oocytes were classified into group A, 662 (50.8%) into group B, and 251 (19.3%) into group C. The fertilization rate of the group B oocytes was significantly higher than for the A and C oocytes. The blastocyst formation rate in group B was significantly higher than in group A. In addition, the pregnancy rate in group B was significantly higher than in the other two groups. CONCLUSION: The oocytes with a spindle size of 90-120 µm2 showed higher fertilization, blastocyst formation, and clinical pregnancy rates than those with larger or smaller spindles. The measurement of the meiotic spindle size thus has a positive predictive value for identifying human embryo developmental potential clinically.

Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

OBJECTIVE: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. STUDY DESIGN: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. RESULTS: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44). CONCLUSION: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.

Relationship between meiotic spindle characteristics in human oocytes and the timing of the first zygotic cleavage after intracytoplasmic sperm injection.

PURPOSE: To investigate the relationship between meiotic spindle characteristics in human oocytes and the timing of the first zygotic cleavage after intracytoplasmic sperm injection (ICSI). METHODS: Zygotes that had cleaved to two-cell stage by 27 h post-ICSI were classified as early cleaving and the remainder as late cleaving. Meiotic spindle parameters previously imaged using the PolScope were compared between the two groups. RESULTS: Of 384 embryos, 163 were classed as early cleaving and 221 as late cleaving. The rate of blastocyst formation or pregnancy by Day 2 embryo transfer was significantly higher following early cleavage than after late cleavage (52.4% vs. 24.4% or 32.6% vs. 11.4%). Spindle areas (108.0 vs. 89.8 µm(2)), lengths (14.7 vs. 13.4 µm) and PolScope retardance were also significantly greater in the early cleaving group. CONCLUSIONS: Meiotic spindle parameters determine the timing of the first zygotic cleavage and are strong indicators of human embryo developmental potential.

Involvement of anticentromere antibody in interference with oocyte meiosis and embryo cleavage.

The aim of this study was to investigate the clinical significance of anticentromere antibody (ACA) among types of antinuclear antibody (ANA) in the properties of oocytes retrieved from infertile women. The rate of metaphase II oocytes or embryo cleavage was significantly decreased in patients with positive ACA compared with patients with negative ACA, suggesting that ACA is an essential marker for flawed oocytes in infertile women with any type of ANA.