Clinical outcomes of personalized blastocyst embryo transfer after endometrial receptivity analysis: A multicenter, retrospective cohort study.

Purpose: To evaluate clinical outcomes after endometrial receptivity analysis (ERA). Methods: This was a multicenter, retrospective cohort study involving 861 women who underwent ERA testing at certified fertility clinics in Japan, and who received subsequent personalized blastocyst embryo transfers (ET) between 2018 and 2020. Clinical outcomes, including pregnancies, miscarriages, and live births, were evaluated according to receptivity status for ERA. Results: Mean patient age was 37.7 years (SD = 4.0), and the median number of previous ETs was 2 (interquartile range, 2-3). 41.0% (353/861) of patients were non-receptive for ERA testing. Clinical pregnancy, miscarriage, and live birth rates for personalized blastocyst ET were 44.5% (226/508), 26.1% (59/226), and 26.8% (136/508) for receptive patients, and 43.1% (152/353), 28.3% (43/152), and 28.9% (102/353) for non-receptive patients, all statistically nonsignificant. Multiple logistic regression demonstrated similar nonsignificant associations between receptivity and clinical outcomes. Greater patient age, smoking, and longer duration of infertility were significantly and negatively associated with receptivity, whereas a history of delivery was positively associated and statistically significant. Conclusions: Clinical outcomes after ERA testing were similar between receptive and non-receptive patients. Further prospective study including an appropriate comparison group are warranted to evaluate the efficacy of ERA testing.

Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility.

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

Does dysbiotic endometrium affect blastocyst implantation in IVF patients?

PURPOSE: To analyze the pregnancy outcomes of IVF patients presenting eubiotic or dysbiotic endometrium at the time of embryo transfer and to analyze what bacterial profiles are suitable for embryo implantation. METHODS: Ninety-nine IVF patients under 40 years old undergoing vitrified-warmed blastocyst transfer in HRT cycle had concurrent endometrial microbiome analysis. Samples from the endometrium were taken from the participants at the time of mock transfer; the bacterial profiles at genus level and percentage of lactobacilli in the endometrium of the patients were analyzed. RESULTS: Thirty-one cases (31.3%) had dysbiotic endometrium. The background profiles, pregnancy rates per transfer (52.9% vs 54.8%), and miscarriage rates (11.1% vs 5.9%) were comparable between patients with eubiotic or dysbiotic endometrium. Major bacterial genera other than Lactobacillus detected in the dysbiotic endometrium were Atopobium, Gardnerella, and Streptococcus. Some patients achieved ongoing pregnancies with 0% Lactobacillus in the endometrium. The endometrial bacterial profiles of pregnant cases with dysbiotic endometrium were comparable with those of non-pregnant cases. CONCLUSION: Analyzing microbiota at the species-level resolution may be necessary for identifying the true pathogenic bacteria of the endometrium and avoiding over-intervention against non-Lactobacillus microbiota. Further studies are necessary for analyzing the mechanism of how the pathogenic bacteria affect embryo implantation.

Effects of fertility preservation in patients with breast cancer: A retrospective two-centers study.

Purpose: To assess the efficacy of fertility preservation (FP) and the impact of chemotherapy on the reproductive potential of Japanese patients with breast cancer. Methods: Sixty-two patients with breast cancer visited the authors' centers from October, 2003 to June, 2015. They were divided into two groups according to the treatment: oocyte or embryo vitrification for FP before cancer treatment (group A) or infertility treatment after cancer treatment (group B). Group B was divided into two subgroups, B1 (no chemotherapy) and B2 (postchemotherapy), in order to analyze the effect of anticancer drugs on ovarian reserves and assisted reproductive technology outcomes. The number of retrieved oocytes, vitrified oocytes or embryos, and pregnancy rates were analyzed and compared: group A compared to group B1 compared to group B2. Results: The patients in groups A and B1 underwent egg collection without any chemotherapy. The numbers of collected oocytes and vitrified embryos were significantly higher in groups A and B1 than in group B2. Nearly 50% of the in vitro fertilization patients who underwent an embryo transfer (ET) became pregnant, including two patients in group A who underwent a vitrified-warmed ET. Among the pregnant women, 70% did not have chemotherapy. Conclusion: For patients with breast cancer, FP with unfertilized oocytes or embryos before chemotherapy seems to be promising for achieving higher pregnancy rates, with no risk of minimal residual disease.

Residual ethylene glycol and dimethyl sulphoxide concentration in human ovarian tissue during warming/thawing steps following cryopreservation.

There have been 60 births after transplantation of cryopreserved ovarian tissue: 58 using the slow freezing method, and two using the vitrification method. DMSO and EG are widely used as cryoprotectants. However DMSO is a known epimutagen, and EG has been reported to be toxic in high concentrations. In this study, we measured residual DMSO and EG in ovarian tissue after vitrification and slow freezing. Cryoprotectants remained at a high concentration in the vitrified/warmed ovarian tissue just before transplantation (DMSO: 9.8 mg/g, EG: 9.8 mg/g). We must consider the impact of the cryoprotectants on the mother and the baby.

Oxygen consumption rate of early pre-antral follicles from vitrified human ovarian cortical tissue.

The study of human ovarian tissue transplantation and cryopreservation has advanced significantly. Autotransplantation of human pre-antral follicles isolated from cryopreserved cortical tissue is a promising option for the preservation of fertility in young cancer patients. The purpose of the present study was to reveal the effect of vitrification after low-temperature transportation of human pre-antral follicles by using the oxygen consumption rate (OCR). Cortical tissues from 9 ovaries of female-to-male transsexuals were vitrified after transportation (6 or 18 h). The follicles were enzymatically isolated from nonvitrified tissue (group I, 18 h of transportation), vitrified-warmed tissue (group II, 6 and 18 h of transportation) and vitrified-warmed tissue that had been incubated for 24 h (group III, 6 and 18 h of transportation). OCR measurement and the LIVE/DEAD viability assay were performed. Despite the ischemic condition, the isolated pre-antral follicles in group I consumed oxygen, and the mean OCRs increased with developmental stage. Neither the transportation time nor patient age seemed to affect the OCR in this group. Meanwhile, the mean OCR was significantly lower (P < 0.05) in group II but was comparable to that of group I after 24 h of incubation. The integrity of vitrified-warmed primordial and primary follicles was clearly corroborated by the LIVE/DEAD viability assay. These results demonstrate that the OCR can be used to directly estimate the effect of vitrification on the viability of primordial and primary follicles and to select the viable primordial and primary follicles from vitrified-warmed follicles.

A live birth from vitrified-warmed oocytes in a Philadelphia chromosome-positive acute lymphoid leukemia patient 5 years following allogenic bone marrow transplantation and after a magnitude 9.0 earthquake in Japan.

PURPOSE: To report a live birth from vitrified-warmed oocytes for a Philadelphia chromosome-positive acute lymphoid leukemia (Ph-ALL) patient. METHODS: A 20-year-old single woman with Ph-ALL requested oocyte cryopreservation at a private fertility clinic using assisted reproduction technology (ART). In cases of leukemia, there is a very short time before chemotherapy, follwed shortly by total body irradiation (TBI), and although she had already received the chemotherapy, ten oocytes were vitrified and stored for 59 months before warming. Soon after the oocyte cryopreservation, she received TBI and bone marrow transplant (BMT). During the storage, a magnitude 9.0 earthquake occurred making oocyte transport necessary. The embryo transfer was planned in a hormone replacement cycle, and intracytoplasmic sperm injection (ICSI) was performed on the vitrified-warmed oocytes. On day 3, two embryos were transferred. RESULTS: The patient became pregnant and delivered a healthy girl after ICSI using vitrified-warmed oocytes. CONCLUSIONS: Oocyte cryopreservation is the best option for fertility preservation of young single women with leukemia. Oncologists and gynecologists who conduct ART should cooperate to improve the quality of life of cancer patients.

Potential indications for ovarian autotransplantation based on the analysis of 5,571 autopsy findings of females under the age of 40 in Japan.

Ovarian cryopreservation and autotransplantation could be of potential value for preservation of fertility in the patients with various malignancies. Ovarian tissue should be cryopreserved actively for fertility preservation, but stored tissue should be autotransplanted with much caution until reliable methods are established to detect minimal residual disease in grafts in precise and reproducible manners.

Incidental testicular cancers that subsequently developed in oligozoospermic and azoospermic patients: report of three cases.

OBJECTIVE: To examine whether infertile men with poor semen count subsequently developed testicular cancers and to describe their clinical presentation. DESIGN: We reviewed 460 male patients with abnormal semen counts between 1989 and 2004. SETTING: University hospital. PATIENT(S): Infertile men who developed testicular cancers after assisted reproductive technologies (ART). INTERVENTION(S): Description of patient characteristics: age at infertility, presentation, semen quality, and ART. MAIN OUTCOME MEASURE(S): The number of patients who subsequently developed testicular cancers and the period from ART to the development of clinical testicular cancers. RESULT(S): Of the 460 patients, 169 patients presented with mild oligozoospermia, 117 patients with severe oligozoospermia, and 174 patients with azoospermia. The follow-up periods were as follows: 1-192 months (median, 96.5 mo) for mild oligozoospermia, 1-156 months (median, 78.5 mo) for severe oligozoospermia, and 1-197 months (median, 99 mo) for azoospermia. We subsequently found three testicular cancers that had developed among severely oligozoospermic and azoospermic patients. The period from the claim of sterility to developing testicular cancers varied from 4 to 14 years (median, 9 y). CONCLUSION(S): These results indicate that severe semen abnormality may be a risk factor in developing testicular cancers. Self-examination of the testes could be used as an alternative or supplement to physical examination and testicular ultrasound as part of the infertility workup, even after ART.

Successful pregnancy and delivery following combined treatment of in vitro maturation (IVM) and testicular sperm extraction (TESE): a case report.

PURPOSE: To report the efficacy of the combined treatment of in vitro maturation (IVM) and testicular sperm extraction (TESE). METHODS: A couple in which the wife had polycystic ovarian syndrome and the husband had severe oligozoospermia. Oocytes were cultured in vitro for maturation followed by oocytes pickup with natural cycle, and TESE was undergone for husband. Matured oocytes were fertilized by intracytoplasmic sperm injection, and two embryos were transferred to wife's uterine. RESULTS: This case was achieved during pregnancy and delivery of a healthy female infant. CONCLUSIONS: The combined treatment of IVM and TESE was effective for this couple's specific infertility factors.

Successful pregnancy outcome using sperm from severely diseased men with testicular cancer and collagen disease: Three case reports.

Objective: To confirm the feasibility of using fresh or frozen/thawed spermatozoa from cancer and collagen diseased patients for intracytoplasmic sperm injection (ICSI). Patients: Two participants were diagnosed with testicular carcinoma and one patient was diagnosed with collagen disease. Methods: Of the two carcinoma patients, one patient provided a fresh testicular biopsy sample and one patient ejaculated fresh sperm after surgical operation. One collagen diseased patient's sperm was frozen, and three samples were used in subsequent ICSI treatment cycles. Their female partners underwent controlled ovarian hyperstimulation for the retrieval of oocytes. Results: Two patients with testicular cancer and their respective partners achieved successful pregnancies from ICSI using fresh sperm after surgery. The patient suffering from collagen disease had a successful pregnancy from ICSI using sperm frozen prior to chemotherapy treatment. Conclusions: Patients with testicular carcinoma or collagen disease who might desire to father children in the future should be offered sperm preservation prior to the initiation of chemotherapy treatment. Under currently available treatment, patients with cases of severe disease can still become biological fathers. (Reprod Med Biol 2004; 3: 69-75).

Successful delivery following cryopreservation of zygotes produced by in vitro matured oocytes retrieved from a woman with polycystic ovarian syndrome-like disease: a case report.

PURPOSE: To estimate frozen zygotes, which developed from in vitro matured oocytes retrieved from polycystic ovarian syndrome-like disease. METHODS: Oocyte retrieval was performed on Day 15 following withdrawal bleeding. The oocytes were incubated for 24 h in TCM-199 maturation medium supplemented with follicle fluid, E2, FSH, and hCG. RESULTS: A total of 12 immature oocytes were collected. Seven of the 12 oocytes (58.3%) developed to the metaphase-II stage, and subsequently, all seven fertilized oocytes were frozen at the pronuclear stage. The remaining five oocytes failed to develop to the metaphase-II stage after an additional 24 h of incubation. Three of seven cryopreserved oocytes were thawed and developed to 2-8-cell cleaved stage embryos. The first pregnancy failed. However, the second frozen-thawed embryo transfer resulted in the delivery of healthy twins. CONCLUSIONS: Successful delivery using frozen zygotes from an anovulatory woman with polycystic ovarian syndrome-like disease.