Healthy live births from transfer of low-mosaicism embryos after preimplantation genetic testing for aneuploidy.

PURPOSE: This study evaluated the potential viability of embryos with low mosaicism level (< 50%) by comparing the clinical outcomes of single mosaic versus euploid blastocyst transfer. In addition, the live birth outcomes for various types of mosaicism with respect to abnormalities in chromosome structure and content were analyzed. METHODS: This study included patients who underwent in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A). The PGT-A cycles performed through next-generation sequencing with single euploid or mosaic embryo transfers were included. We collected 299 frozen single embryo transfer cycles-216 single euploid and 83 mosaic-between July 2016 and July 2018. This study analyzed clinical outcomes, including fetal karyotyping by using amniocentesis, gestational age at delivery, and live birth weight after single mosaic embryo transfer. RESULTS: The average birth weight of infants in the euploid and mosaic blastocyst transfer groups was 3146.2 and 2997.7 g, respectively. The karyotyping results of prenatal diagnosis in all pregnant women were normal. Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism. No significant difference was observed between infants from euploid and mosaic blastocyst transfers. CONCLUSION: If patients have no euploid embryos, mosaic embryos can be transferred as they have potential for implantation and development into euploid healthy infants. This study is invaluable for counseling clinical results after single mosaic embryo transfers.

Effects of growth hormone plus gonadotropins on controlled ovarian stimulation in infertile women of advanced age, poor responders, and previous in vitro fertilization failure patients.

OBJECTIVE: To investigate the effects of growth hormone (GH) cotreatment in ovarian stimulation in infertile women of advanced age, poor responders, and patients with one or more previous IVF treatment failures. MATERIALS AND METHODS: We conducted a retrospective observational study of 436 patients undergoing GH cotreatment in ovarian stimulation. The first arm included 134 infertile women of advanced age. The second arm included 236 patients with one or more IVF previous treatment failures, and the third arm included 66 younger poor responders. Main outcome measures were the number of oocytes and embryos, quality of embryos, and implantation and pregnancy rates. RESULTS: In infertile women of advanced age, GH plus ovarian stimulation yielded no statistical differences in the numbers of oocytes and embryos, quality of embryo, and rates of implantation and pregnancy. In the second arm, the mature oocyte number (8.2 vs. 6.8), implantation rate (16.1% vs. 0%), and pregnancy rate (33.9% vs. 0%) in the GH cotreatment group differed significantly from those in the control group; the rate of good-quality embryos in the GH cotreatment group improved from 35.5% ± 31.1%-41.4% ± 30.6% in this arm. Similar results were observed in the third arm; in this arm, the clinical pregnancy rate was 30.3% in the GH cotreatment group and 6.1% in the control group. CONCLUSION: No significant differences were observed in infertile women of advanced age, which may be due to the low GH dose. The GH adjuvant therapy for patients with one or more previous IVF treatment failures and for poor responders significantly improved the oocyte and embryo numbers as well as implantation and pregnancy rates.

Evaluation of telomere length in cumulus cells as a potential biomarker of oocyte and embryo quality.

STUDY QUESTION: Is the relative telomere length in cumulus cells associated with embryo quality and the subject's age? SUMMARY ANSWER: The relative telomere length in cumulus cells at the time of oocyte collection may be a new potential biomarker for selecting highly competent oocytes and good quality embryos. WHAT IS KNOWN ALREADY: Telomeres play central roles in aging and in determining cell fate. In mammalian ovarian follicles, maturing oocytes are nurtured and supported by surrounding somatic cells, the mural granulosa and cumulus cells. STUDY DESIGN, SIZE, DURATION: A total of 350 oocyte-cumulus complex samples were collected from 80 IVF cycles prospectively recruited for this study at the Lee Women's Hospital, Taichung, Taiwan. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulus cells were manually separated from the oocyte-cumulus complex under a microscope. DNA was extracted from cumulus cells and assessed for telomere length by real-time quantitative PCR. We analyzed telomere length relative to a single copy marker gene (36B4) to evaluate the effect of the real reproductive age of cumulus cells on oocyte and embryo development. MAIN RESULTS AND THE ROLE OF CHANCE: The relative telomere length was longer in cumulus cells from mature oocytes compared with cumulus cells from immature oocytes, and in cumulus cells from good-quality embryos compared with cumulus cells from poor-quality embryos. The cut-off value of the T/S ratio between good and poor-quality embryos on embryonic Day 3 was 4.235. LIMITATIONS, REASONS FOR CAUTION: Only a limited number of cumulus cells were measured for each oocyte and the corresponding embryo. WIDER IMPLICATIONS OF THE FINDINGS: The relative telomere length in cumulus cells at the time of oocyte collection is predictive of highly competent oocytes and good-quality embryos but may not be sufficiently discriminating to be clinically useful. STUDY FUNDING/COMPETING INTEREST(S): National Science Council, Taiwan (NSC 97-2314-B-040-018). The authors have no conflicts of interest to declare.

The pregnancy health and birth outcomes of women who underwent assisted reproductive technology: Results of a national survey.

BACKGROUND: There is an upward trend for parents to resort to assisted reproductive technology (ART) treatment due to delayed childbirth or birth difficulties. OBJECTIVE: This study investigates the pregnancy health and birth outcomes of women who underwent ART and analyzes the factors that influence birth weight to become<10 percentile when undergoing ART. MATERIALS AND METHODS: This study analyzed results of the first wave of the Taiwan Birth Cohort study. Through stratified systematic sampling, 24,200 mother-and-child sampling pairs were obtained from a total of 206,741 live births in Taiwan in 2005; 366 of the babies were born with the use of ART. RESULTS: During pregnancy, mothers who used ART suffered from higher risks of complication than the natural conception counterparts, including gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH), and placenta previa. Additionally, babies born through ART had poorer outcomes than the natural conception groups: the low birth weight (<2500g) was 33.1% compared to 6.4% for babies born naturally. CONCLUSION: Pregnancy health and birth outcomes of women who underwent ART were worse than those who got natural conception. Types of maternal complication among ART women included GDM, PIH, and placenta previa. Having multiple births was the most important factor that causes low birth weight in babies. The results of this study can be used as a reference for the health and care of mothers and babies who use ART.

Association of creatin kinase B and peroxiredoxin 2 expression with age and embryo quality in cumulus cells.

PURPOSE: the purpose of this study was to identify age-related oocyte or embryo markers suitable for non-invasive analysis, as women over 38 years of age experience diminished pregnancy and ovulation rates. METHODS: we used real-time quantitative PCR to examine the gene expression profiles in cumulus cells acquired from older and younger age groups. We selected 11 genes involved in three functions that directly affect cellular aging: cell cycle control, apoptosis, and metabolism. RESULTS: CKB and PRDX2 were up-regulated in women older than 38 years, and the expression of these genes in cumulus cells was associated with embryo quality. In good-quality embryos, CKB expression was higher in the cumulus cells acquired from both older and younger age groups than in poor-quality embryos. CONCLUSIONS: these potential relationships among cumulus cell gene expression, oocyte quality, and age may expand our understanding of oogenesis and embryo development. CKB and PRDX2 may serve as biomarkers or therapeutic targets for the developmental potential of oocytes.

Blastocoel volume is related to successful establishment of human embryonic stem cell lines.

Human embryonic stem cell (hESC) banks strive to establish hESC lines from discarded or surplus human embryos. The effect of embryo quality on establishing hESC lines was investigated by observing cultures derived from 28 Taiwanese fresh surplus and donated embryos that were cultured using the whole embryo method. Cultures of hESC lines were followed for 15 months. At the blastocyst stage, 14 of the 28 embryos were graded as good quality, defined as featuring a blastocoel volume of at least half of the embryo volume. Fourteen embryos did not meet these standards on day 5. Five successful hESC lines were derived from the good quality embryos (5/14; 35.7%); these hESC cells grew for 27-60 passages. In contrast, cells from poor quality embryos all stopped growing at the second or third passage. The successful hESC exhibited typical stem cell characteristics, including the capacity for pluripotent differentiation. Embryo quality on day 5, as defined by blastocoel volume, is thus a strong predictor for successful establishment of hESC lines.

Recipient age and pulsatility index affect uterine receptivity in oocyte donation programmes.

Successful embryo implantation depends on interactions between the embryo and the uterus. Investigating factors related to the recipients in an oocyte donation programme could therefore improve the overall pregnancy outcome. In this study, the factors that affect outcomes following IVF after oocyte donation were evaluated in a retrospective cohort study. A total of 143 cycles were evaluated. All oocyte donors were younger than 30 years of age. In the youngest recipients (< 34 years old) the implantation rate was higher (P = 0.042) and the abortion rate was apparently lower than in the recipients of more advanced age (> or =40 years old). The implantation and pregnancy rates were higher when the pulsatility index was > or = 3.0. The pulsatility index on the day of embryo transfer in oocyte donation IVF cycles was an important determinant of successful pregnancy outcomes.

A comparison of the outcomes between twin and reduced twin pregnancies produced through assisted reproduction.

OBJECTIVE: To compare the outcome of twin pregnancies, derived from IVF cycles, with and without fetal reduction. DESIGN: A retrospective cohort study. SETTING: The IVF Division of the Lee Women's Hospital, Taiwan. PATIENT(S): Seven hundred forty-two twin pregnancies, including 389 nonreduced pregnancies, 353 of which resulted from fetal reduction. INTERVENTION(S): Selective fetal reduction for high-order multiple pregnancies. MAIN OUTCOME MEASURE(S): The rates of extreme prematurity and prematurity (i.e., less than 28 and 36 weeks gestational age, respectively), frequency of birth weight discordance, mean birth weight of twins, neonatal mortality, and morbidity. RESULT(S): The fetal reduction group was associated with a higher incidence of extreme prematurity, prematurity, and lower birth weight than the nonreduced group, although the impact was relatively small. These findings were more pronounced among patients with a higher initial number of fetuses. The rates of discordant birth weights between the two groups were not significantly different. CONCLUSION(S): High-order multiple pregnancies after fetal reduction is still associated with a mild increased risk of premature delivery and low birth weight when compared to nonreduced twin pregnancies. These results provide an additional reason to limit the number of embryos transferred during IVF.