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.
There is a long-held credo, as illustrated in Langman's Medical Embryology (11th ed., Sadler, 2010), that dichorionic diamniotic (DD) twins develop after embryo splitting in the early stages of ...embryonic development. However, from our clinical experiences of the examination of data from single-embryo transfers in 16 fertility clinics in Japan and from various reports, the majority of occurrences of DD twins have been found in the blastocyst stages.
Purpose
The present study aimed to analyze the pregnancy outcomes of IVF patients presenting Lactobacillus‐dominated microbiota (LDM) or non‐Lactobacillus‐dominated microbiota (NLDM) of their ...endometrium and to report cases who were treated for NLDM concurrently with antibiotics and prebiotic/probiotic supplements in a Japanese infertile population.
Methods
Ninety‐two IVF patients were recruited from August 2017 to March 2018. Endometrial fluid samples for sequencing were collected using an IUI catheter. The bacterial status of the endometrium and the pregnancy outcomes were analyzed. For cases with NLDM, antibiotics and prebiotics/probiotics were administered according to their individual microbial conditions.
Results
Forty‐seven cases (51.1%) presented LDM and 45 cases (48.9%) presented NLDM at initial analysis. Nine Patients with NLDM were treated by antibiotics and prebiotics/probiotics, and successfully became Lactobacillus‐dominant. Pregnancy rates by single vitrified‐warmed blastocyst transfers were higher in the LDM group (58.9% per patient and 36.3% per FBT) than in the NLDM group (47.2% per patient and 34.7% per FBT) but not significantly different.
Conclusion
The results of this study could not necessarily prove the clear benefit of establishing Lactobacillus‐dominated endometrium in terms of pregnancy outcome, but there is significance in searching for endometrial microbial status of infertile patients and recovering Lactobacillus‐dominated endometrium might benefit implantation.
This is a follow‐up to the previous study, analyzing the endometrial microbiome of IVF patients and assessing the pregnancy outcome of patients with Lactobacillus‐dominant or non‐Lactobacillus‐dominant endometrium, and we found that Lactobacillus dominancy may be beneficial for the pregnancy outcome of IVF patients. Also, we tried to establish a treatment strategy for recovering Lactobacillus‐dominant endometrium, and this may be the first study reporting on a treatment for dysbiotic endometrium. We found that concurrent administration of antibiotics and prebiotics and/or probiotics was successful in recovering endometrium to a Lactobacillus‐dominant condition.
Aim
This study aimed to assess the efficacy of the endometrial receptivity array (ERA) as a diagnostic tool and the impact of personalized embryo transfer (pET) for the treatment of patients with ...recurrent implantation failure (RIF) in Japan.
Methods
Fifty patients with a history of RIF with frozen‐thawed blastocyst transfers were recruited from July, 2015 to April, 2016. Endometrial sampling for the ERA and histological dating and a pET according to the ERA were performed. The receptive (R) or non‐receptive (NR) status of the endometrium as a result of the first ERA, endometrial dating, and pregnancy rates after the pET were analyzed.
Results
Of the patients with RIF, 12 (24%) were NR. Among them, eight (66.7%) were prereceptive. A clinical follow‐up was possible in 44 patients who underwent the pET. The pregnancy rates were 58.8% per patient and 35.3% per first pET in the R patients and 50.0% per patient and 50.0% per first pET in the NR patients. Discrepancies between the ERA results and histological dating were seen more in the NR patients than in the R patients.
Conclusions
For patients with unexplained RIF, there is a significance in searching for their personal window of implantation (WOI) using the ERA, considering the percentage of those who were NR and the pregnancy rates that resulted from the pET. By transferring euploid embryos in a personal WOI, much better pregnancy rates are expected.
Human-assisted reproductive technologies (ART) are a widely accepted treatment for infertile couples. At the same time, many studies have suggested the correlation between ART and increased ...incidences of normally rare imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Silver-Russell syndrome (SRS). Major methylation dynamics take place during cell development and the preimplantation stages of embryonic development. ART may prevent the proper erasure, establishment, and maintenance of DNA methylation. However, the causes and ART risk factors for these disorders are not well understood.
A nationwide epidemiological study in Japan in 2015 in which 2777 pediatrics departments were contacted and a total of 931 patients with imprinting disorders including 117 BWS, 227 AS, 520 PWS, and 67 SRS patients, were recruited. We found 4.46- and 8.91-fold increased frequencies of BWS and SRS associated with ART, respectively. Most of these patients were conceived via in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and showed aberrant imprinted DNA methylation. We also found that ART-conceived SRS (ART-SRS) patients had incomplete and more widespread DNA methylation variations than spontaneously conceived SRS patients, especially in sperm-specific methylated regions using reduced representation bisulfite sequencing to compare DNA methylomes. In addition, we found that the ART patients with one of three imprinting disorders, PWS, AS, and SRS, displayed additional minor phenotypes and lack of the phenotypes. The frequency of ART-conceived Prader-Willi syndrome (ART-PWS) was 3.44-fold higher than anticipated. When maternal age was 37 years or less, the rate of DNA methylation errors in ART-PWS patients was significantly increased compared with spontaneously conceived PWS patients.
We reconfirmed the association between ART and imprinting disorders. In addition, we found unique methylation patterns in ART-SRS patients, therefore, concluded that the imprinting disorders related to ART might tend to take place just after fertilization at a time when the epigenome is most vulnerable and might be affected by the techniques of manipulation used for IVF or ICSI and the culture medium of the fertilized egg.
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.
Background and Aims: Excess lactate in culture medium accumulates may adversely affect the embryo as metabolic stress. The purpose of this study is to investigate whether culture media with a ...low-lactate concentration have an effect on embryonic development in IVF. Method: A split sibling study was performed on 8313 oocytes from 1,312 ICSI cycles from which at least two matured oocytes were retrieved from January 2020 through August 2022. Sperm-injected oocytes were allocated to Continuous Single Culture-NX (NX, N=4352) which contains a low concentration of lactate (1mM) and Global Ⓡ total Ⓡ LP (GL, N=3961), which contains 5mM concentration of lactate. Patients were classified into subgroups of <40 years (854 cycles) and Formula: see text40 years (458 cycles). Single frozen embryo transfers were performed in 859 cycles (NX; N = 500, GL; N = 359). Embryo development up to Day 6, clinical pregnancy and miscarriage rates were compared. Usable blastocysts were defined as any blastocyst cryopreserved on day 5 or day 6. P<0.05 was considered statistically significant. Results: The mean patient age was 37.1 ± 4.4 years. Overall fertilization rates and the blastocyst development rate were significantly higher in NX than GL (80.7% vs. 78.9% and 62.3% vs. 59.8% respectively). There was no significant difference in blastocyst utilization rate on day 5 with all ages considered (36.2% NX vs. 34.2% GL). There was no significant difference in blastocyst development rate for patients Formula: see text40 years, but for patients Formula: see text40 years, blastocyst development rate and day 5 usable blastocyst rate were significantly increased in NX (51.2% vs. 46.4% and 26.2% vs. 22.4% respectively). There were no significant differences in the clinical pregnancy or miscarriage rates (48.8% vs. 49.9% and 22.1% vs. 21.8% respectively). Conclusion: Our results suggest that the lower concentration of lactate in culture medium is effective for late embryonic development in advanced maternal age patients.
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.
Purpose
Increasing numbers of women are opting to undergo non‐medical oocyte cryopreservation (NMOC). In this report, we present experience at our clinic and discuss NMOC in Japan.
Methods
We ...followed the progress of 403 women who underwent NMOC at our clinic between 2014 and 2021, totaling 592 reproductive cycles.
Results
In total, 61 women underwent oocyte warming and fertility treatment. Of these, 13 women gave birth to 14 children. The median age at first oocyte cryopreservation was 38.3 years, and the oldest pregnant woman was 42 years. Most clients (60%) were in their late 30s. The median time between first oocyte cryopreservation and warming was 3.0 years. One woman was able to achieve a live birth with four vitrified oocytes.
Conclusions
This is the first report in Japan documenting pregnancies and childbirths resulting from NMOC. Ideally, women hope to achieve natural pregnancy between 20 and 32 years of age. NMOC is an option for individuals who are unable to pursue pregnancy during optimal reproductive years and wish to preserve their fertility for future attempts. NMOC is recommended in cases with few indications, and it is necessary to continue accumulating data on its long‐term safety and effectiveness.
Background: It is important to select blastocysts based on their likelihood of leading to pregnancy. The purpose of this study was to focus on expansion time and blastocyst diameter as simple factors ...to assess blastocysts relative to clinical outcomes. Methods: This study is based on 1,514 cycles in women Formula: see text years who underwent frozen-thawed blastocyst transfer (FBT) between November 2017 and February 2021. Blastocysts were classified according to the time they reached Formula: see textm inner diameter (116, 120, and 140Formula: see texth). Furthermore, blastocyst diameter at freezing was classified into three groups: groups S (under 167Formula: see textFormula: see textm), M (167–181Formula: see textFormula: see textm), and L (over 181Formula: see textFormula: see textm), based on tertile values. We compared the clinical outcomes (including the clinical pregnancy rate CPR) of FBT. Results: CPR was significantly higher in groups M and L than in group S at 116Formula: see texth (Formula: see text). At 120Formula: see texth, CPR in group L was significantly higher than in group S (Formula: see text). However, at 140Formula: see texth, there were no significant differences among the three groups. There were no significant differences in miscarriage rates at 116, 120, and 140Formula: see texth. When only good quality embryos were compared, group L resulted in a significantly higher CPR than group S at 116Formula: see texth (Formula: see text). At 120Formula: see texth, both groups M and L had significantly higher CPR than group S (Formula: see text). There were no significant differences at 140Formula: see texth. Conclusion: These results suggest that when multiple embryos are frozen at the same time on day 5 of culture, a higher pregnancy rate can be obtained by selecting embryos with larger blastocyst diameters. In addition, it is important to confirm sufficient blastocyst expansion before cryopreservation.
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