Vaginal yolk sac tumor resected by a novel laparo/endoscope-assisted posterior sagittal approach: a case report.

BACKGROUND: Yolk sac tumor (YST) is a germ cell tumor that is generally associated with good prognosis in children. It has been recently reported that vaginal YSTs can be cured using chemotherapy alone. Thus, minimal invasiveness and function preservation are pre-requisites for surgical approaches. Herein, we report a case of vaginal YST that was resected in a function-preserving manner using a unique combination of surgical approaches. CASE PRESENTATION: In a 9-month-old Asian female infant, a vaginal tumor was detected while investigating for vaginal bleeding. The patient was referred to our hospital, and the tumor was diagnosed as a YST after incisional biopsy. Six courses of carboplatin-based chemotherapy were administered. Contrary to the findings in previous reports, the tumor was chemo-resistant and surgical resection was required for the residual tumor. During surgery, we utilized laparoscopic and endoscopic procedures to ensure tumor-free surgical margins at the cervix, rectum, and lateral wall of the vagina. Additionally, the posterior sagittal approach was used to easily resect the tumor, and the vagina was reconstructed leaving only inconspicuous scars in the intergluteal cleft. No complications occurred postoperatively. Pathological examination of the surgical specimen revealed tumor-free surgical margins. The patient received four cycles of intensified chemotherapy before and after the surgery. The patient has been disease-free for 6 months now. CONCLUSIONS: Our combination of laparo/endoscopic and posterior sagittal approach ensured a tumor-free macroscopic surgical margin with easier, cosmetically pleasing vaginal reconstruction, while preserving the anorectal and urinary functions. We believe that this approach could be utilized not only for vaginal YST, but also for any vaginal tumor, especially those arising from the posterior or lateral wall.

Spatiotemporal perturbations of pronuclear breakdown preceding syngamy affect early human embryo development: a retrospective observational study.

PURPOSE: During fertilisation, female and male pronuclei (PNs) migrate to the centre of the ooplasm, juxtapose, and break down synchronously in preparation for the first mitosis. While PN non-juxtaposition and PN breakdown (PNBD) asynchrony are occasionally observed, their developmental implications remain uncertain. This study investigated the possible relationships among the two phenomena, preimplantation development patterns, and live birth rates in single blastocyst transfers. METHODS: A total of 1455 fertilised oocytes cultured in a time-lapse incubator were retrospectively analysed. Fertilised oocytes were divided into four groups according to the presence of PN juxtaposition and breakdown synchrony. The relationships of abnormal PN behaviour with embryo morphokinetics, blastocyst formation, and live birth were evaluated. RESULTS: PN non-juxtaposition and asynchrony were observed in 1.9% and 1.0% of fertilised oocytes, respectively. The blastocyst cryopreservation rates in the synchronous-non-juxtaposed and asynchronous-non-juxtaposed groups were significantly lower than that in the synchronous-juxtaposed group. The rates of clinical pregnancy, ongoing pregnancy, and live birth were comparable among the groups. Non-juxtaposition was significantly associated with increased trichotomous cleavage at the first cytokinesis (P < 0.0001) and an increase in the time interval from PNBD to first cleavage (P < 0.0001). Furthermore, asynchronous PNBD was significantly correlated with increased rapid cleavage at the first cytokinesis (P = 0.0100). CONCLUSION: Non-juxtaposition and asynchronous PNBD is associated with abnormal mitosis at the first cleavage and impaired preimplantation development. However, embryos displaying abnormal PNBD may develop to blastocyst stage and produce live births, suggesting blastocyst transfer as a more appropriate culture strategy.

Characteristics of the cytoplasmic halo during fertilisation correlate with the live birth rate after fresh cleaved embryo transfer on day 2 in minimal ovarian stimulation cycles: a retrospective observational study.

BACKGROUND: Information regarding the influence of cytoplasmic events during fertilisation on the clinical outcome remains limited. The cytoplasmic halo is one of these events. A previous study that used time-lapse technology found an association of the presence and morphokinetics of the cytoplasmic halo with cleavage patterns, development to the blastocyst stage, and the ongoing pregnancy rate after blastocyst transfer. Therefore, the cytoplasmic halo may be a useful predictor of the pregnancy outcome after cleaved embryo transfer. This study evaluated the ability of the cytoplasmic halo to predict a live birth after fresh cleaved embryo transfer on day 2, and sought to identify factors potentially influencing the presence and morphokinetics of the halo. METHODS: A total of 902 embryos cultured in the EmbryoScope+® time-lapse system and subjected to single fresh cleaved embryo transfer were retrospectively analysed. The presence and duration of a cytoplasmic halo were annotated. The initial positions of the pronuclei were also observed. The correlation between the cytoplasmic halo and live birth was evaluated and the association of the cytoplasmic halo with patient, cycle, and embryonic characteristics was determined. RESULTS: Absence of a cytoplasmic halo was associated with a significant decrease in the likelihood of a live birth after fresh cleaved embryo transfer. Prolongation of the halo, especially the duration of central repositioning of cytoplasmic granules, had an adverse impact on the live birth rate. The characteristics of the cytoplasmic halo were not affected by the ovarian stimulation method used, female age, the serum steroid hormone level on the day of trigger, or semen quality. However, the cytoplasmic halo was significantly affected by male age, oocyte diameter, and the initial position of the male pronucleus. CONCLUSIONS: Absence or prolongation of the cytoplasmic halo was negatively correlated with the live birth rate after fresh cleaved embryo transfer. The characteristics of the cytoplasmic halo were strongly associated with oocyte diameter, male age, and the initial position of the male pronucleus. These findings indicate that the characteristics of the cytoplasmic halo can be used to select more competent embryos for transfer at the cleavage stage.

Successful endoscopic surgical treatment of pleuroperitoneal communication in two infant cases.

BACKGROUND: Pleuroperitoneal communication (PPC) is an uncommon, but potentially life-threatening complication of peritoneal dialysis (PD). If a fistula does not close with conservative treatment, surgical repair is required. However, approximately half of these patients are forced to shift from PD to hemodialysis. Although it is important to confirm the site of the fistula to achieve a successful surgical treatment, this identification is more difficult in pediatric patients than in adults. CASE PRESENTATION: We report two infantile cases of severe PPC associated with PD. In both cases, the age at onset was less than 2 years, and right-sided pleural effusion with dyspnea was observed. PPC was diagnosed by the change in color of the pleural fluid after the injection of a dye into the peritoneal cavity. Peritoneal scintigraphy and single-photon emission computed tomography and computed tomography (SPECT/CT) were performed, and these were effective in locating the fistula site. Endoscopic surgery (video-assisted thoracic surgery (VATS) and laparoscopic surgery) was performed. Indocyanine green (ICG), which was injected into the abdominal cavity, showed the exact site of the fistula. The fistula was successfully closed by attaching an absorbable sheet to it from the thoracic side and an autograft (the falciform ligament) to it from the abdominal side in one patient. In the other patient, the fistula site was resected and sutured, and reinforced with an absorbable sheet. In both cases, PD was resumed without any complication. CONCLUSION: We successfully treated two infants of PPC by endoscopic surgery. To identify the fistula site, the ICG navigation method was useful. Even in small infants, PPC can be treated successfully by endoscopic surgical repair if the site of the fistula is identified.

Effects of fatty acid supplementation during vitrification and warming on the developmental competence of mouse, bovine and human oocytes and embryos.

RESEARCH QUESTION: Does fatty acid supplementation in vitrification and warming media influence developmental competence in oocytes after vitrification and warming? DESIGN: Mouse oocytes and four-cell embryos were vitrified and warmed with solutions supplemented with fatty acid and cultured to the blastocyst stage. To study lipid metabolism after vitrification, quantitative real-time polymerase chain reaction was used to analyse the expression of genes related to beta oxidation in mouse embryos vitrified and warmed with or without fatty acids. The effects of fatty acid supplementation in the warming solutions on the developmental competence of bovine and human embryos were analysed. Blastocyst outgrowth assay was used to evaluate the potential of human blastocysts for adhesion to fibronectin. RESULTS: The neutral lipid content of mouse oocytes in the fatty acid 1% supplementation group was significantly higher than in the fatty acid 0% group (P = 0.0032). The developmental rate to the blastocyst stage was significantly higher in the fatty acid 1% group than in the fatty acid 0% group in mice (P = 0.0345). Fatty acid supplementation in warming solution upregulated Acaa2 and Hadha in mouse embryos. Fatty acids significantly improved the developmental ability of bovine embryos to the blastocyst stage (P = 0.0048). Warming with 1% fatty acid supplementation significantly increased the proportion of human blastocysts with morphological grade A inner cell mass (P = 0.0074) and trophectoderm (P = 0.0323). CONCLUSIONS: Fatty acid supplementation in the warming solutions improved the developmental competence of vitrified-warmed mouse oocytes by activating the beta-oxidation pathway. Fatty acid supplementation enhanced the developmental rate of bovine embryos to the blastocyst stage and improved morphological characteristics of human embryos vitrified at the cleavage stage.

Analysis of clinical factors and reasons that influence the disposition of cryopreserved embryos in Japanese patients with infertility treated in our clinic.

AIM: To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. METHODS: Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. RESULTS: The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. CONCLUSION: Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

Prolactin receptor expression and its role in trophoblast outgrowth in human embryos.

RESEARCH QUESTION: What is the gene expression pattern of prolactin receptor (PRLR) in human pre-implantation embryos and what are its functions during the embryonic development and adhesion process? DESIGN: A total of 405 discarded human vitrified oocytes and embryos donated for research by consenting couples were used in this study. The oocytes and embryos were used to analyse PRLR expression and to evaluate the influence of prolactin (PRL) supplementation in the embryo culture medium on embryo developmental competence and viability. The rates of blastocyst development and adhesion, outgrowth area, cytoskeletal reorganization and nascent adhesion formation were compared between groups. RESULTS: PRLR expression increased significantly after embryo compaction (P < 0.0001) and blastulation (P < 0.0001). Supplementation of the embryo culture medium with PRL did not improve the developmental rate and morphological grade. In contrast, blastocyst outgrowth was significantly increased in embryos cultured with PRL (P = 0.0004). Phosphorylation of JAK2, downstream of the prolactin receptor family, was markedly higher in the PRL-treated embryos than in embryos cultured without PRL. Furthermore, the expression of mRNAs encoding ezrin-radixin-moesin proteins and epithelial-mesenchymal transition-related genes was stimulated by the activation of PRL-JAK2 signalling. The PRL-treated embryos had higher mRNA expression of integrins than non-treated embryos, and transcriptional repression of cadherin 1 was observed after PRL treatment. More nascent adherent cells expressed focal adhesion kinase and paxillin in PRL-treated embryos than in non-treated embryos. CONCLUSIONS: Human embryos express PRLR at the morula and blastocyst stages, and PRLR signalling stimulates blastocyst adhesion by promoting integrin-based focal adhesions and cytoskeletal organization during trophoblast outgrowth.

Anti-Müllerian hormone is correlated with cumulative live birth in minimal ovarian stimulation with clomiphene citrate: a retrospective cohort study.

BACKGROUND: Several studies have investigated the correlation between the serum anti-Müllerian hormone (AMH) level and in vitro fertilization (IVF) outcomes in controlled ovarian stimulation cycles; however, studies regarding the correlation of the serum AMH level with IVF outcomes in minimal ovarian stimulation cycles remain limited. In this study, we aimed to analyze the correlation of the serum AMH level with ovarian responsiveness, embryonic outcomes, and cumulative live birth rates in clomiphene citrate (CC)-based minimal ovarian stimulation cycles. METHODS: Clinical records of 689 women whose entire ovarian stimulation regimen consisted solely of minimal stimulation cycle IVF using CC alone from November 2017 to October 2019 were retrospectively reviewed. The association between IVF outcomes and the serum AMH level before the initiation of the first fertility treatment was analyzed. Furthermore, the correlation of the serum AMH level with cumulative live birth rates after IVF treatment was assessed. The Cochran-Armitage test, Pearson's chi-squared test, Spearman rank correlation test, Student's t-test, one-way analysis of variance, logistic regression analysis, Kaplan-Meier method and Cox proportional hazards model were used to analyze the data. RESULTS: The serum AMH level positively correlated with the number of retrieved oocytes, blastocyst formation rate, blastocyst cryopreservation rate, and live birth rate per oocyte retrieval in CC-based minimal ovarian stimulation cycles without any exogenous gonadotropin administration. Furthermore, the cumulative live birth rate and treatment period required for conceiving were strongly associated with the serum AMH level at the initiation of fertility treatment. CONCLUSIONS: A low serum AMH level correlated with low ovarian responsiveness, impaired pre-implantation embryonic development, and decreased cumulative live birth rate in CC-based minimal ovarian stimulation cycles. Therefore, the cycle success rate would be predicted by measuring the serum AMH level in minimal ovarian stimulation with CC alone.

Establishment of day 7 blastocyst freezing criteria using blastocyst diameter for single vitrified-warmed blastocyst transfer from live birth outcomes: a single-center, large cohort, retrospectively matched study.

PURPOSE: To establish blastocyst freezing criteria for day 7 blastocyst (day 7 BL) for single vitrified-warmed blastocyst transfer (SVBT) by examining the diameter of blastocysts. METHODS: Patients who underwent day 7 BL transfer cycles (1143 cycles, mean age: 38.5 ± 3.5) and randomly selected patients after 1:1 matching who underwent day 6 BL transfer cycles and day 2-single-embryo transfer (SET) cycles were used for analysis. Comparison of the miscarriage (per clinical pregnancy) and live birth rates were made among day 2-SET, day 7 BL, and day 6 BL. These blastocyst groups were stratified into six groups based on blastocyst diameter, namely, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, for making the freezing criteria. RESULTS: For each diameter, 180 µm, 190 µm, 200 µm, 210 µm, over 220 µm, and hatched, the live birth rates of day 7 BL after SVBT were 9.0%, 11.9%, 11.5%, 15.6%, 20.0%, and 19.9%, respectively. Compared with the 14.6% live birth rate of the day 2-SET group, the live birth rate of 220 µm day 7 BL was significantly higher (P < 0.05) and was around the same in other diameter groups. CONCLUSION: Our study demonstrates that sufficient live birth rates can be obtained after SVBT even from blastocysts on day 7 when blastocysts were vitrified at expanded blastocyst stage of over 180 µm of diameter or at hatched blastocyst stage and were transferred at the optimal time. This is the first study to establish a day 7 blastocyst freezing criteria using blastocyst diameter, which is an objective assessment way.

Cytoplasmic halo characteristics during fertilization and their implications for human preimplantation embryo development and pregnancy outcome.

RESEARCH QUESTION: Is the spatiotemporal phenomenology of the cytoplasmic halo during fertilization related to embryonic competence? DESIGN: Time-lapse images from 1009 zygotes were retrospectively analysed from 560 patients who underwent IVF with minimal stimulation and single vitrified-warmed blastocyst transfer between April 2017 and March 2018. Halo presence and morphokinetics were monitored and compared relative to embryo quality, blastocyst expansion and ongoing pregnancy. RESULTS: Halo was observed in 88% of fertilized oocytes. Embryos derived from zygotes without halo had significantly higher rates of rapid cleavage (P = 0.0004), cell fusion (P = 0.0028) and asymmetrical division (P = 0.0002) compared with those derived from zygotes with halo. Multivariate logistic regression analysis had significantly higher developmental rates compared with the expanded blastocyst stage in embryos displaying a halo, regardless of its distribution (adjusted odds ratio 0.435; P = 0.0004). Prolonged halo time intervals were significantly correlated with increased asymmetrical division at first cell division (P = 0.0412, P = 0.0088, respectively) and decreased developmental rates to expanded blastocyst stage (P = 0.0062, P = 0.0020, respectively). Additionally, prolonged presence of the cytoplasmic halo was associated with a decreased ongoing pregnancy rate (adjusted odds ratio 0.871; P = 0.006). Poor sperm quality and decreased oocyte diameter were correlated with absence of the cytoplasmic halo (P = 0.0477, P < 0.0001, respectively) or prolonged halo presence (P = 0.0139, P = 0.0002, respectively). CONCLUSIONS: Halo presence and morphokinetics are associated with cleavage patterns, development to blastocyst stage and ongoing pregnancy rate after single blastocyst transfer. Halo morphokinetics seems to reflect sperm and oocyte quality. Cytoplasmic halo might be valuable predictor for refining selection of more developmentally competent blastocysts.

Effects of gonadotropin administration on clinical outcomes in clomiphene citrate-based minimal stimulation cycle IVF.

PURPOSE: Exogenous gonadotropins (EGn) have been used occasionally in clomiphene citrate (CC)-based minimal stimulation cycles to compensate insufficient secretion of endogenous gonadotropin; however, the effectiveness of EGn supplementation remains unknown. In the present study, we assessed whether EGn improved pregnancy outcomes in CC-based minimal stimulation cycles. METHODS: A total of 223 patients treated with CC and EGn (CC-EGn group) were matched one to one to patients treated with CC only (CC group) by propensity score matching. Embryonic and pregnancy outcomes were retrospectively compared between the groups. RESULTS: The numbers of retrieved oocytes, fertilized oocytes, cleaved embryos, and cryopreserved blastocysts were increased in the CC-EGn group compared with the CC group. However, the cumulative live birthrate was comparable between the two groups. Although the increased number of retrieved oocytes was correlated significantly with improvement of the cumulative live birthrate in both groups, the correlation tended to be lower in the CC-EGn group than in the CC group (odds ratio, 1.193 vs 1.553). CONCLUSIONS: In CC-based minimal stimulation cycles, the stimulation should be started with CC only, and EGn administration should be scheduled only if insufficient secretion of endogenous gonadotropin is observed in the late follicular phase.

Does the endometrial thickness on the day of the trigger affect the pregnancy outcomes after fresh cleaved embryo transfer in the clomiphene citrate-based minimal stimulation cycle?

PURPOSE: Thin endometrium is often observed after clomiphene citrate (CC) administration for follicular development and is one of the reasons for embryo transfer (ET) cancelation or implantation failure. We retrospectively analyzed whether the endometrial thickness (EMT) on the days of the maturation trigger and ET are predictive factors of pregnancy outcomes after fresh cleaved ET in a CC-based minimal stimulation cycle (CC-cycle). METHODS: A total of 746 CC-cycles in vitro fertilization (IVF), followed by fresh cleaved ET, from November 2018 to March 2019 were analyzed. Associations between the pregnancy outcomes and EMT on the days of the trigger and ET were statistically evaluated. RESULTS: Although the EMT on the day of ET was not significantly associated with the ongoing pregnancy rate (adjusted odds ratio [AOR], 1.043; P = .3251), a decreased EMT on the day of the trigger was significantly associated with a low ongoing pregnancy rate (AOR, 1.154; P = .0042). Furthermore, the clinical pregnancy rate was significantly lower when the EMT was <7 mm on the day of the trigger during the CC-cycle. CONCLUSIONS: These results suggest that measurement of the EMT on the day of the trigger could be effective for predicting the pregnancy outcomes after fresh cleaved ET during the CC-cycle.

Endometrial thickness on the day of the LH surge: an effective predictor of pregnancy outcomes after modified natural cycle-frozen blastocyst transfer.

STUDY QUESTION: Can the endometrial thickness (EMT) on the day of the LH surge predict pregnancy outcomes after single vitrified-warmed blastocyst transfers (SVBTs) in modified natural cycles? SUMMARY ANSWER: Decreased EMT on the day of the LH surge is associated with older female age and a shortened proliferation phase and may be associated with low live birth and high chemical pregnancy rates. WHAT IS KNOWN ALREADY: The relation between EMT on the day of embryo transfer (ET) and pregnancy outcomes remains controversial; although numerous studies reported an association between decreased EMT on the day of ET and a reduced likelihood of pregnancy, recent studies demonstrated that the EMT on the day of ET had limited independent prognostic value for pregnancy outcomes after IVF. The relation between EMT on the day of the LH surge and pregnancy outcomes after SVBT in modified natural cycles is currently unknown. STUDY DESIGN SIZE DURATION: In total, 808 SVBTs in modified natural cycles, performed from November 2018 to October 2019, were analysed in this retrospective cohort study. Associations of EMT on the days of the LH surge with SVBT and clinical and ongoing pregnancy rates were statistically evaluated. Clinical and ongoing pregnancy rates were defined as the ultrasonographic observation of a gestational sac 3 weeks after SVBTs and the observation of a foetal heartbeat 5 weeks after SVBTs, respectively. Similarly, factors potentially associated with the EMT on day of the LH surge, such as patient and cycle characteristics, were investigated. PARTICIPANTS/MATERIALS SETTING METHODS: The study includes IVF/ICSI patients aged 24-47 years, who underwent their first SVBT in the study period. After monitoring follicular development and serum hormone levels, ovulation was triggered via a nasal spray containing a GnRH agonist. After ovulation was confirmed, SVBTs were performed on Day 5. The EMT was evaluated by transvaginal ultrasonography on the day of the LH surge and immediately before the SVBT procedure. MAIN RESULTS AND THE ROLE OF CHANCE: Of the original 901 patients, 93 who were outliers for FSH or proliferative phase duration data were excluded from the analysis. Patients were classified according to quartiles of EMT on day of the LH surge, as follows: EMT < 8.1 mm, 8.1 mm ≤ EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.6 mm and EMT ≥ 10.6 mm. Decreased EMT on day of the LH surge was associated with lower live birth (P = 0.0016) and higher chemical pregnancy (P = 0.0011) rates. Similarly, patients were classified according to quartiles of EMT on day of the SVBT, as follows: EMT < 9.1 mm, 9.1 mm ≤ EMT < 10.1 mm, 10.1 mm ≤ EMT < 12.1 mm and EMT ≥ 12.1 mm. A decreased EMT on the day of SVBT was associated with a lower live birth rate (P = 0.0095) but not chemical pregnancy rate (P = 0.1640). Additionally, multivariate logistic regression analysis revealed a significant correlation between EMT on day of the LH surge and ongoing pregnancy; however, no correlation was observed between EMT on the day of SVBT and ongoing pregnancy (adjusted odds ratio 0.952; 95% CI, 0.850-1.066; P = 0.3981). A decreased EMT on day of the LH surge was significantly associated with greater female age (P = 0.0003) and a shortened follicular/proliferation phase (P < 0.0001). LIMITATIONS REASONS FOR CAUTION: The data used in this study were obtained from a single-centre cohort; therefore, multi-centre studies are required to ascertain the generalisability of these findings to other clinics with different protocols and/or patient demographics. WIDER IMPLICATIONS OF THE FINDINGS: This is the first report demonstrating a significant correlation between EMT on day of the LH surge and pregnancy outcomes after frozen blastocyst transfer in modified natural cycles. Our results suggest that EMT on day of the LH surge may be an effective predictor of the live birth rate. STUDY FUNDING/COMPETING INTERESTS: This study was supported by resources from the Kato Ladies Clinic. The authors have no conflicts of interest to declare.

Success rates in minimal stimulation cycle IVF with clomiphene citrate only.

PURPOSE: To determine age-adjusted overall success rates for patients undergoing clomiphene citrate only minimal stimulation cycle (mini) in vitro fertilization (IVF) without any gonadotropin administration. METHODS: Eight hundred thirty-nine women (mean age: 38.4 ± 0.1 years; 2488 cycles) underwent clomiphene citrate only mini-IVF. Their first oocyte retrieval was between January 2009 and December 2009, with follow-up until December 2014. The cumulative live birth rate (CLBR) per oocyte retrieval cycle started and live birth rate per oocyte was retrospectively analyzed. The basic CLBR was calculated as the number of women who achieved a live birth divided by the total number of women who started oocyte retrieval. RESULTS: The mean number of oocytes retrieved was 1.5. The basic CLBRs for all ages after the first and third cycles were 22.6% and 39.2%, respectively. For ≤ 34 years, 35-37 years, 38-40 years, 41-42 years, and ≥ 43 years, CLBRs after the first and third cycles were 42.5% and 70.1%, 32.9% and 49.1%, 20.0% and 38.6%, 12.6% and 25.2%, and 4.4% and 8.8%, respectively. These rates had a significant relationship with age (P < 0.01). The LBR per oocyte for all ages was 9.6%. CONCLUSION: Acceptable overall IVF success rates can be achieved in clomiphene citrate only mini-IVF, as well as acceptable LBR. The CLBRs and LBRs per oocyte are evidently influenced by women's age.

Evaluation of uterine receptivity after gonadotropin releasing hormone agonist administration as an oocyte maturation trigger: a rodent model.

In natural cycle or minimal stimulation cycle IVF, buserelin acetate (buserelin), a gonadotropin-releasing hormone agonist, is often used as a maturation trigger; however, its effect on pregnancy outcomes remains unclear. Therefore, in the present study, we compared uterine receptivity in buserelin-administered mice with that in human chorionic gonadotropin (hCG)-administered mice during the peri-implantation period. Implantation, decidualisation, and term-pregnancy were impaired following hCG, but not buserelin administration. hCG stimulated the synthesis and secretion of progesterone and oestradiol, whereas ovarian steroidogenesis in the buserelin-treated group was comparable with that in the control group. Furthermore, similar to the observation in controls, the buserelin-treated group exhibited activation of progesterone receptor signalling and inhibition of oestrogen receptor signalling in the endometrial epithelium on the day of implantation. However, epithelial progesterone signalling was not detected, and a high expression of genes downstream to oestrogen was observed on day 4 following hCG administration. These results suggest that buserelin administration does not impact uterine receptivity as it did not affect ovarian steroidogenesis and endometrial steroid signalling. Therefore, buserelin is preferred as an oocyte maturation trigger to optimise uterine receptivity during treatments involving timed intercourse, intrauterine insemination, or fresh embryo transfer following in vitro fertilisation.

Blastomere movement post first cell division correlates with embryonic compaction and subsequent blastocyst formation.

BACKGROUND: Blastomere movement (BMov) occurs after the first cell division in human embryos. This movement has been suggested as a prognostic parameter for pregnancy outcome prediction following cleavage-stage embryo transfer. However, the effect of BMov on preimplantation development and pregnancy outcome after blastocyst transfer remains unclear. Therefore, this study aimed to evaluate whether BMov after the first cell division is correlated with blastocyst formation rate and live birth rate after single vitrified-warmed blastocyst transfer (SVBT). METHODS: Nine hundred and sixty-six embryos cultured in the EmbryoScope+® time-lapse system were retrospectively analyzed. The BMov type was categorized into three groups; namely, bouncing, wobbling, and twist-and-crumble. The BMov duration (dBMov) between the first (t2) and second cell division (t3) was monitored, and the ratio of dBMov to the duration of the 2-cell stage was calculated [dBMov/(t3-t2)]. Developmental rates to the 4-cell, 8-cell, morula, blastocyst, and expanded blastocyst stages were assessed, as well as blastocyst morphological grade. The correlations between dBMov and clinical pregnancy, ongoing pregnancy, and live birth rates were evaluated. RESULTS: Increased dBMov/(t3-t2) was significantly correlated with decreased developmental rates to the 8-cell, morula, blastocyst, and expanded blastocyst stages, especially from the 4-cell stage to the morula stage. Analysis of different types of BMov revealed that embryos with bouncing movement exhibited significantly higher developmental rates to the 8-cell, morula, blastocyst, and expanded blastocyst stages compared with embryos with twist-and-crumble movement. The morphological quality of blastocyst-stage embryos with twist-and-crumble movement was significantly lower than that of embryos with bouncing and wobbling movements. The rates of clinical pregnancy, ongoing pregnancy, and live birth after SVBT were not correlated with BMov type or duration. CONCLUSIONS: Embryonic compaction and subsequent blastocyst formation are adversely affected by twist-and-crumble movement and prolonged movement after the first cell division. Our results indicate that the preimplantation developmental competence of human embryos could be predicted by assessing BMov after the first cell division on day 1.

Closed embryo culture system improved embryological and clinical outcome for single vitrified-warmed blastocyst transfer: A single-center large cohort study.

While some studies have shown that the closed embryo culture system (CCS) is a possible improvement over standard embryo culture systems (STS) in terms of early embryonic development, information on clinical outcomes of culturing blastocysts following single vitrified-warmed blastocyst transfer (SVBT) in the CCS and STS remains limited. Therefore, the objective of this single-center, large-cohort, retrospective study was to compare embryonic development until the blastocyst stage and clinical outcomes following SVBT between CCS and STS. From May 2017 to October 2018, 2420 oocytes from 1402 patients who underwent in vitro fertilization and blastocyst culture after minimal stimulation were divided into two groups (CCS and STS). The main outcome measures in the two groups were embryological (blastocyst formation rates and utilized blastocyst rates) and clinical outcomes (ongoing pregnancy rates) after a single vitrified-warmed blastocyst transfer (SVBT). There were no significant differences in the blastocyst formation rates between the CCS and STS groups (59.6% versus 59.1%, p = 0.81). However, there were significant differences in utilized blastocyst rates (51.0% versus 46.6%, p < 0.05). Ongoing pregnancy rates per SVBT cycle were significantly higher in the CCS group than in the STS group (41.4% versus 34.4%, p < 0.05). Moreover, after applying multivariable logistic regression analysis, the type of embryo culture system (CCS to STS, adjusted odds ratios: 1.41, 95% CI: 1.04-1.91) was correlated with ongoing pregnancy. Our study suggests that compared to STS, CCS could improve utilized blastocyst rates and ongoing pregnancy rates to a greater extent, following SVBT.

Prolonged blastomere movement induced by the delay of pronuclear fading and first cell division adversely affects pregnancy outcomes after fresh embryo transfer on Day 2: a time-lapse study.

RESEARCH QUESTION: What is the incidence, origin and clinical significance of blastomere movement after the first cell division in the human embryo? DESIGN: A total of 1096 embryos, cultured in the EmbryoScope+ ® time-lapse system and subjected to a single fresh cleaved embryo transfer, were retrospectively analysed. Type and duration of blastomere movement (dBMov) between the first (t2) and second cell division (t3) was monitored, and the ratio of dBMov during the 2-cell stage [dBMov/(t3-t2)] was calculated. Morphological evaluation of embryos was performed by referring to the size of the blastomere and fragmentation after first division in addition to Veeck's criteria on Day 2. The correlation between dBMov and ongoing pregnancy was evaluated and the association of dBMov with patient and embryonic characteristics was determined. RESULTS: Both movement type and the value of dBMov/(t3-t2) were significantly associated with asymmetrical first division, fragment formation and morphological grade on Day 2. Multivariate logistic regression analysis revealed that a higher value of dBMov/(t3-t2) significantly correlated with a decreased ongoing pregnancy rate, even after adjustment for co-founders (odds ratio 0.399, P = 0.0419). The time intervals of pronuclear (PN) alignment and PN fading were significantly correlated with the dBMov/(t3-t2) value. CONCLUSIONS: Embryos with extended blastomere movement after the first cell division, which is associated with the delay of PN fading and first cell division, have a lower competence to initiate an ongoing pregnancy after fresh embryo transfer on Day 2. Thus, blastomere movement could be a useful predictive parameter for selecting embryos at the early cleavage stage.

Lack of a meaningful association between dietary patterns and in vitro fertilization outcome among Japanese women.

PURPOSE: The purpose of this study was to examine whether preconception maternal dietary pattern is associated with in vitro fertilization (IVF) outcome among Japanese women. METHODS: This prospective study included 140 Japanese women who underwent conventional-IVF/intracytoplasmic sperm injection. The patients' diets during the previous month before egg retrieval were assessed with validated brief-type self-administered diet history questionnaire. Dietary patterns from 33 predefined food groups [energy-adjusted food (g/1000 kcal)] were extracted by factor analysis. The primary outcome measure was clinical pregnancy rate after IVF. RESULTS: Thirty-six women had confirmed clinical pregnancy. Three dietary patterns were identified: "Vegetable and seafood," "Western," and "Rice and miso soup." The "Vegetables and seafood" dietary pattern (high intakes of green and other vegetables, mushrooms, seasoning, fish, soy products, chicken, and potatoes) was not associated with clinical pregnancy ([odds ratio per one-quartile increase in dietary pattern: 0.94 (95% confidence interval: 0.67-1.32), P = 0.73]. This relationship was unaltered after controlling for potential confounders. Furthermore, no association was seen between the other two dietary patterns and clinical pregnancy. CONCLUSIONS: The three maternal preconception dietary patterns identified revealed no meaningful association with IVF outcome in Japanese women. Further studies in various populations with different dietary patterns are needed to confirm these findings.

Cryostorage duration does not affect pregnancy and neonatal outcomes: a retrospective single-centre cohort study of vitrified-warmed blastocysts.

A retrospective cohort study of 8736 autologous single vitrified-warmed blastocyst transfer cycles was conducted in a single centre to investigate the effect of cryostorage on clinical and neonatal outcomes. Cryostorage duration was classified into three groups: (A) 0-2 months (n = 4702); (B) 2-13 months (n = 2853) and (C) 13-97 months (n = 1181). Blastocysts were vitrified using the Cryotop method. No significant differences were observed in live birth rates: (A) 37.3%; (B) 34.9%; (C) (35.2%). Gestational period was significantly shorter in group C: (A) 38.7 ± 1.8; (B) 38.6 ± 1.6; (C) 38.1 ± 1.7; P < 0.05. This was clinically unimportant as the average gestational age was more than 38 weeks. No significant differences between groups were observed in birth weight: (A) 3060 ± 455 g; (B) 3052 ± 449 g; (C) 2992 ± 445 g, or congenital malformation rates: (A) 2.2%; (B) 1.9%; (C) 1.8%. The limitation of this study was that maximum storage duration was 8 years; most blastocysts were in cryostorage for much shorter periods. Long-term storage of blastocysts that are vitrified using an open device vitrification system has no negative effect on pregnancy and neonatal outcomes.