PGT-A is Associated with Reduced Live Birth Rates in Fresh but not Frozen Donor Oocyte IVF cycles: An Analysis of 18,562 Donor Cycles Reported to SART CORS.

OBJECTIVE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte IVF cycles. DESIGN: Retrospective cohort study of the SART CORS database. SUBJECTS: 11,348 fresh and 7,214 frozen-thawed donor oocyte IVF cycles were analyzed. EXPOSURE: The first reported donor stimulation cycle per patient between January 1, 2014 and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014 and December 31, 2016, were included in the study. MAIN OUTCOME MEASURES: LBR was compared for patients using fresh and frozen-thawed donor oocytes, with or without PGT-A. Logistic regression models were adjusted for age, body mass index, gravidity, infertility etiology, and prior IVF cycles. RESULTS: Among patients who had blastocysts available for transfer or PGT-A, use of PGT-A was associated with a decreased first transfer LBR (46.9 vs 53.2%, p <0.001) and CLBR (58.4 vs 66.6%, p <0.001) in fresh oocyte donor cycles compared with no PGT-A. LBR in frozen-thawed oocyte donor cycles with PGT-A were nominally higher than those without PGTA (48.3% vs. 40.5%) but were not statistically significant in multivariable logistic regression models (p=0.14). Early pregnancy loss was not significantly different with and without PGT-A. Multiple gestation, preterm birth, and low birthweight infants were all reduced with addition of PGT-A in fresh donor oocyte cycles, though these outcomes were not significantly different when comparing single embryo transfers in fresh oocyte cycles and also not significantly different among frozen-thawed donor oocyte cycles. CONCLUSION: PGT-A in fresh oocyte donor cycles was associated with decreased LBR and CLBR, while effects on frozen-thawed oocyte donor cycles were clinically negligible. Obstetrical benefits associated with PGT-A in fresh donor cycles appear linked to increased single embryo transfer.

In vitro fertilization and perinatal outcomes of patients with advanced maternal age after single frozen euploid embryo transfer: a propensity score-matched analysis of autologous and donor cycles.

OBJECTIVE: To evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in patients with advanced reproductive age after undergoing single frozen euploid embryo transfer. DESIGN: A multicenter, retrospective, cohort study. SETTING: University-affiliated and private IVF centers. PATIENT(S): Patients aged 39-46 years who underwent IVF with intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy using whole-chromosome sequencing with donor (n = 278) or autologous (n = 278) oocytes between October 2017 and October 2021. INTERVENTION(S): Single frozen euploid embryo transfer with donor or autologous euploid embryo. MAIN OUTCOME MEASURE(S): The main outcome measure was the live birth rate (LBR) after the first embryo transfer, calculated per embryo transfer. The secondary outcomes included the implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birth weight at the time of delivery. RESULT(S): Patients using donor or autologous oocytes had a similar likelihood of implantation (57.91% [51.87-63.78] vs. 57.19% [51.15-63.09]) and LBR (41.01% [95% confidence interval {CI}, 35.17-47.04] vs. 42.45% [95% CI, 36.56-48.49]). Furthermore, there were no significant differences in the ectopic pregnancy rate (0.72% [0.09-2.57] vs. 0.36% [0.01-1.99]), miscarriage rate (16.19% [12.06-21.05] vs. 14.39% [95% CI, 10.48-19.08]), gestational age (38.50 [38.08-38.92] vs. 39.16 [38.25-40.07] weeks), or birth weight of infants (2,982.25 [2,606.69-3,357.81] vs. 3,128.24 [2,962.30-3,294.17] kg). The univariate analysis showed no association between advanced maternal age and the LBR (relative risk, 1.03 [95% CI, 0.84-1.25]). Multivariate analysis using putative confounders for embryo competency found no associations with LBR (adjusted relative risk, 1.22 [95% CI, 0.75-1.98]). CONCLUSION(S): Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in the LBR, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birth weight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with women with advanced reproductive age undergoing IVF are heavily driven by embryonic aneuploidy.

Impact of adenomyosis on in vitro fertilization outcomes in women undergoing donor oocyte transfers: a prospective observational study.

OBJECTIVE: To prospectively examine the association between adenomyosis type, location, and severity with reproductive outcomes in patients undergoing single embryo transfer (SET) with embryos derived from donor oocytes. DESIGN: A prospective observational cohort study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Patients with infertility with (n = 114) and without (n = 114) adenomyosis who received their first donor oocyte transfer between January 2019 and January 2023 were included in this study. INTERVENTIONS: Adenomyosis was confirmed with the presence of at least one direct feature visualized by 2- or 3-dimensional transvaginal ultrasound and classified according to type (diffuse or focal), localization (inner or outer myometrium and/or junctional zone [JZ]), and uterine extension (mild, moderate, or severe). After an artificial or natural endometrial preparation cycle, patients underwent SET in the blastocyst stage. MAIN OUTCOME MEASURES: The primary outcome was the implantation rate. The secondary outcomes were the clinical pregnancy, live birth, and miscarriage rates after SET. RESULTS: The presence of adenomyosis did not significantly affect the implantation, clinical pregnancy, or live birth rates. However, women with adenomyosis had a significantly higher miscarriage rate than those without adenomyosis (35.4% vs. 18.1%, respectively). The multivariate analysis assessed possible risk factors for each clinical outcome considered in the study and showed that adenomyosis affected the risk of miscarriage. Specifically, transvaginal sonography detection of adenomyosis in the JZ was associated with over threefold higher relative risk of miscarriage (relative risk [RR], 3.28; 95% confidence interval [CI], 1.38-7.78). Conversely, adenomyosis features detected exclusively in the outer myometrium were associated with a higher ongoing pregnancy rate (RR, 0.30; 95% CI, 0.13-0.72). Diffuse adenomyosis in the JZ and severe adenomyosis increased the relative risk of miscarriage two-fold (RR, 2.29; 95% CI, 1.22-4.30 and RR, 2.20; 95% CI, 1.19-4.04, respectively). CONCLUSIONS: This study demonstrated that although adenomyosis did not significantly reduce the odds of implantation, the direct signs of adenomyosis in the JZ and disease severity are significant risk factors for miscarriage in patients receiving donor oocyte transfers. This study highlights the importance of thorough ultrasound examination and detailed adenomyosis classification in the assessment and management of patients with infertility.

Preventable Hazards from in Vitro Fertilization - A Case Series of CF Patients from Bulgaria.

Pre-implantation genetic diagnosis (PGD) is not often performed when donor gametes are used, due to its high cost. This is with the presumption that the donors are healthy. We report on five cases of babies with confirmed cystic fibrosis (CF), being the result from in vitro fertilization (IVF) with donor (4 cases) or own gametes (one case). There has been no family history for CF in any of the families affected. The clinical presentation in the children ranged from meconium ileus to recurrent respiratory infections and severe nasal polyposis. The age of diagnosis also varied from birth until 9 years. Since one of the presented cases was discovered in a very renowned private IVF clinic, the clinic changed their own protocol, and currently they test every donor for CF carriership. The percentage of CF carriers in the donor population is roughly the same as the one predicted in the general population of Bulgaria - 1/33. Although PGD is costly, the costs for proper care for a CF patient are currently much higher. The more economical option would to screen every donor for CF carriership. IVF requires a lot of physical and psychological stamina. The couples that go through this procedure also require a great deal of hope. It is essential to be more preconscious for possible congenital diseases. We advocate every IVF center to test the donors for CF carriership or to provide PGD for their clients.

All that glitters is not gold: a stereological study of human donor oocytes.

Here we report a quantitative analysis of human metaphase II (MII) oocytes from a 22-year-old oocyte donor, retrieved after ovarian-controlled hyperstimulation. Five surplus donor oocytes were processed for transmission electron microscopy (TEM), and a stereological analysis was used to quantify the distribution of organelles, using the point-counting technique with an adequate stereological grid. Comparisons between means of the relative volumes (Vv) occupied by organelles in the three oocyte regions, cortex (C), subcortex (SC) and inner cytoplasm (IC), followed the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction. Life cell imaging and TEM analysis confirmed donor oocyte nuclear maturity. Results showed that the most abundant organelles were smooth endoplasmic reticulum (SER) elements (26.8%) and mitochondria (5.49%). Significant differences between oocyte regions were found for lysosomes (P = 0.003), cortical vesicles (P = 0.002) and large SER vesicles (P = 0.009). These results were quantitatively compared with previous results using prophase I (GV) and metaphase I (MI) immature oocytes. In donor MII oocytes there was a normal presence of cortical vesicles, SER tubules, SER small, medium and large vesicles, lysosomes and mitochondria. However, donor MII oocytes displayed signs of cytoplasmic immaturity, namely the presence of dictyosomes, present in GV oocytes and rare in MI oocytes, of SER very large vesicles, characteristic of GV oocytes, and the rarity of SER tubular aggregates. Results therefore indicate that the criterion of nuclear maturity used for donor oocyte selection does not always correspond to cytoplasmic maturity, which can partially explain implantation failures with the use of donor oocytes.

Pregnancy outcomes with donor oocyte embryos in patients diagnosed with adenomyosis using the Morphological Uterus Sonographic Assessment criteria.

OBJECTIVE: To use the Morphological Uterus Sonographic Assessment (MUSA) criteria to evaluate the impact of adenomyosis on the live birth rate after donor egg embryo transfer. DESIGN: Retrospective cohort study. SETTING: Tertiary fertility care center. PATIENT(S): A total of 100 patients who received 223 donor embryo transfers from January 2014-2020. All patients underwent ultrasound before their first transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Our study was powered (80%) to assess the primary outcome of live birth rate; the secondary outcomes included the clinical pregnancy, biochemical pregnancy, and miscarriage rates. RESULT(S): Only 22 of 100 patients were diagnosed with adenomyosis on the original ultrasound report. When the MUSA criteria were applied, 76 patients had at least 1 possible ultrasonographic feature of adenomyosis; all 76 patients had an interrupted junctional zone. The second most common feature of adenomyosis was a globular and/or enlarged uterus (89.4%). Adjusted modeling demonstrated that a single ultrasound feature, 2 or more features, specific features, or the location of features did not affect the live birth outcome. A per-centimeter increase in the diameter of focal lesions was significantly associated with a decrease in the odds of live birth by the factor of 0.91. CONCLUSION(S): To our knowledge, our study is the first to characterize adenomyosis using the MUSA criteria in the donor oocyte population. Overall, our data were reassuring in that the ultrasonographic features of adenomyosis may not impact reproductive outcomes. However, we identified that the location and size of focal lesions may be important and should be studied further.

Factors affecting live birth rates in donor oocytes from commercial egg banks vs. program egg donors: an analysis of 40,485 cycles from the Society for Assisted Reproductive Technology registry in 2016-2018.

OBJECTIVE: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate and cumulative LBR for SET using donor oocytes. RESULT(S): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs. CONCLUSION(S): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved.

Evaluating the Contribution of Oocyte, Sperm, and Uterus in Determining the Outcome of Intracytoplasmic Sperm Injection - A Retrospective Observational Comparative Study on Intracytoplasmic Sperm Injection using Own Oocytes and Donor Oocytes.

CONTEXT: Several studies have assessed the contribution of oocyte, sperm, and endometrium on the outcome of intracytoplasmic sperm injection (ICSI) separately. This study assesses the relative contribution of oocyte, sperm, and uterus in achieving clinical pregnancy (CP) through ICSI by comparing own and third-party ICSI cycles. AIM: The aim of the study is to evaluate and compare the strength of contribution of oocyte, sperm, and uterus in achieving CP through ICSI. SETTINGS AND DESIGN: This retrospective observational study of ICSI cycles for 20 months including 1000 embryo transfers (ETs). METHODOLOGY: Subjects were divided into two groups, Group 1 - ICSI with own oocytes (550 ETs) and Group 2 - ICSI with donor oocytes (450 ETs). Both the groups had 3 subgroups - a (husband sperm, transferred to self), b (donor sperm, transferred to self), c (husband sperm, transferred to a gestational surrogate). CP rate (CPR) as a major outcome was studied in the groups and subgroups. STATISTICAL ANALYSIS: CPR was compared between various subgroups using Z-test and Chi-square of significance of difference between proportions. A P < 0.05 was taken as the level of statistical significance. RESULTS: CPR in subgroup 1a < 35 years, 1a ≥35 years, and 2a was 42.98%, 26.21%, and 40.92%, respectively (P = 0.001). CPR was compared between 2a and 2c (40.92%, 56.5%, P = 0.044) and between 2a and 2b (40.92%, 42.11%, P = 0.866). Implantation rate was highest in Group 2c (34.88%) compared to other subgroups. CONCLUSION: The higher CPR in women <35 years undergoing ICSI with own oocytes than older women and a comparable CPR as that of recipients of donor oocytes suggests that age thereby oocyte quality is the strongest determining factor in achieving clinical pregnancy. Among oocyte recipients, higher CPR in surrogate uterus than patient uterus suggests that uterus/endometrium plays a considerable role, and comparable CPR between ICSI using husband sperm and donor sperm indicates that sperm quality might not play a major role in achieving CP.

Important parameters affecting quality of vitrified donor oocytes.

For group of 281 oocytes obtained from 43 stimulated donors and cryopreserved by vitrification protocol using Cryotop and Kitazato medium we determined important parameters of oocytes collection and vitrification processes which strongly affect the probability that warmed oocytes will produce high-quality embryos for transfer. The probability to obtain high-quality embryos for transfer from vitrified and warmed oocytes was highest when two conditions were fulfilled: 1. oocytes were incubated before vitrification for 7-10 h and 2. stimulated ovaries of donors in one cycle produced a smaller number of oocytes (<7 oocytes from one donor per stimulated cycle). The probable reasons for these observations were: 1. early vitrification (less than 7 h) before final oocyte metaphase II maturation negatively affected the crucial process of post-warm remodelling of spindles and chromosomes, which reduced the fertilization and utilization rates, 2. the evaluated vitrification protocol amplifies negative impact of membrane defects of oocytes of those cohorts containing more than 6 oocytes - freezing places great demands on the integrity and elasticity of the cell membranes. The fact that cryopreservation influences a complex state of oocytes was confirmed by confocal microscopy.

Efficiency and efficacy of vitrification in 35 654 sibling oocytes from donation cycles.

STUDY QUESTION: Is oocyte vitrification/warming as efficient and effective as using fresh oocytes in donation cycles? SUMMARY ANSWER: IVF with vitrified donor oocytes is less efficient than using fresh oocytes, but its efficacy remains comparable to that of fresh cycles. WHAT IS KNOWN ALREADY: Oocyte vitrification is used to preserve the reproductive potential of oocytes. A small number of randomized controlled trials carried out by experienced groups have shown that this technique provides fertilization, pregnancy, implantation and ongoing pregnancy rates comparable to those of fresh oocytes. However, large registry-based analyses have consistently reported lower live birth rates (LBRs) in cycles using vitrified oocytes. It is not clear whether this decrease may be due to the effect of vitrification per se on the oocytes or to the lower efficiency of the technique, as some of the oocytes do not survive after warming. STUDY DESIGN, SIZE, DURATION: Retrospective cohort analysis of 1844 cycles of oocyte donation (37 520 oocytes), each donor in the study provided enough oocytes for at least one reception cycle with fresh oocytes (2561 cycles) and one reception cycle with vitrified oocytes (2471 cycles) from the same ovarian stimulation (sibling oocytes). Overall, 35 654 oocytes were considered in the analysis. All embryo transfers (n = 5032) were carried out between 2011 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Differences in reproductive outcomes after the first embryo transfer were evaluated using Pearson's Chi-squared test and regression analysis adjusted for recipient's age, BMI, sperm origin and state, day of embryo transfer, morphological score and number of transferred embryos. We performed two additional sub-analyses, to test whether the efficiency and/or effectiveness of vitrification/warming impacts reproductive results. One analysis included paired cycles where the same number of fresh and vitrified oocytes were available for ICSI (SAME sub-analysis), while the second analysis included those cycles with a 100% survival rate post-warming (SAME100 sub-analysis). MAIN RESULTS AND THE ROLE OF CHANCE: Baseline and cycle characteristics of participants were comparable between groups. Overall, fertilization rates and embryo morphological scores were significantly lower (P < 0.001) when using vitrified oocytes; moreover, vitrified oocytes also resulted in lower reproductive outcomes than sibling fresh oocytes using both unadjusted and adjusted analyses: ongoing pregnancy (32.1% versus 37.5%; P < 0.001; OR 0.88, 95% CI 0.77, 1.00) and live birth (32.1% versus 31.9%; P = 0.92; OR 1.16, 95% CI 0.90, 1.49). However, when the efficiency of warming was taken into account, reproductive outcomes in recipients became comparable: ongoing pregnancy (33.5% versus 34.1%; P = 0.82; OR 1.11, 95% CI 0.87, 1.43) and LBR (32.1% versus 32%; P = 0.97; OR 1.15, 95% CI 0.89, 1.48). Moreover, after selecting only cycles that, in addition to having the same number of oocytes available for ICSI, also had 100% post-warming survival rate in the vitrified group, reproductive outcomes were also comparable between fresh and vitrified oocytes: ongoing pregnancy (34.8% versus 32.4%; P = 0.42; OR 1.32, 95% CI 0.98, 1.77) and live birth (32.9% versus 31.0%; P = 0.52; OR 1.27, 95% CI 0.95, 1.71), indicating that reproductive outcomes of these cycles are affected by the efficiency of the vitrification/warming technique performed rather than the oocyte damage due to the fast cooling process to which oocytes are subjected. LIMITATIONS, REASONS FOR CAUTION: An open vitrification system was used for all cases, and oocyte vitrification/warming was performed by experienced embryologists with consistently high survival rates; caution must be exerted when extrapolating our results to data obtained using other open vitrification systems, closed vitrification systems or to IVF units with survival rates <90%. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest cohort study comparing reproductive outcomes of vitrified and fresh sibling donor oocytes to date. We found that, when the number of oocytes available after warming is equal to the number of fresh oocytes, reproductive results including live birth are comparable. Consequently, the efficiency of vitrification must be taken into account to achieve the same reproductive outcomes as with fresh oocytes. We recommend implementing strict indicators of vitrification/warming efficiency in clinics and refining vitrification/warming protocols to maximize survival. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by intramural funding of Clínica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia (GENCAT 2015 DI 048). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Having a baby in your 40s with assisted reproductive technology: The reproductive dilemma of autologous versus donor oocytes.

BACKGROUND: Increasing numbers of women ≥40 years old are accessing assisted reproductive technology (ART) due to age-related infertility. There is limited population-based evidence about the impact on the cumulative live birth rate (CLBR) of women aged ≥40 years using their own oocytes, compared to women of a similar age, using donor oocytes. AIMS: To compare the CLBR for women ≥40 years undergoing ART using autologous oocytes and women of similar age using donor oocytes. MATERIALS AND METHODS: This population-based retrospective cohort study used data from all women aged ≥40 years undergoing ART with donated (n = 987) or autologous oocytes (n = 19 170) in Victoria, Australia between 2009 and 2016. A discrete-time survival model was used to evaluate the CLBR following ART with donor or autologous oocytes. The odds ratio, adjusted for woman's age; male age; parity; cause of infertility; and the associated 95% confidence intervals (CI), were calculated. The numbers needed to be exposed (NNEs) were calculated from the adjusted odds ratio (aOR) and the CLBR in the autologous group. RESULTS: The CLBR ranged from 28.6 to 42.5% in the donor group and from 12.5% to 1.4% in the autologous group. The discrete-time survival analysis with 95% CI demonstrated significant aOR on CLBR across all ages (range aOR: 2.56, 95% CI: 1.62-4.01 to aOR: 15.40, 95% CI: 9.10-26.04). CONCLUSIONS: Women aged ≥40 years, using donor oocytes had a significantly higher CLBR than women using autologous oocytes. The findings can be used when counselling women ≥40 years about their ART treatment options and to inform public policy.

Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes.

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction. Euploidy rates in egg donor cycles undergoing PGT-A (N = 423) were examined retrospectively for associations with donor age, gonadotropin doses (dose per day), the fraction of gonadotropin provided by hMG (F(hMG)), days of stimulation, estradiol per mature oocyte on day of trigger, number of mature oocytes retrieved, number of embryos biopsied, incidence of euploidy and physician of record. Differences in euploidy rates between physicians were examined using analysis of variance. The proportion of euploid embryos per donor cycle was examined for associations with COH parameters using pairwise post-hoc comparisons, adjusting for multiple testing. The set of variables from this analysis was then submitted to a principal component analysis. Linear regression analysis was used to assess the relationships between stimulation parameters and the incidence of euploidy (the dependent variable). Euploidy rates and cycle parameters varied significantly among treating physicians. Euploidy rates (expressed as a fraction of biopsied embryos) were associated (p = 0.01) only with the F(hMG) but not with the number of MII retrieved or other variables. On the other hand, the number of euploid embryos (in contrast to the euploidy rate) was associated with the number of MII produced. Donor euploidy rates are significantly associated with the fraction of total gonadotropin comprising human menopausal gonadotropin (or F(hMG)) during controlled ovarian hyperstimulation but are not associated with other cycle parameters. The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos.

Unique Associations between Insulin-Like Growth Factor Binding Protein-1, Insulin-Like Growth Factor-1 and T Cell Immunoglobulin Mucin 3 in Successful Twin Pregnancies Conceived with Donor Oocytes.

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.

Prevalence of structural birth defects in IVF-ICSI pregnancies resulting from autologous and donor oocytes in Indian sub-continent: Results from 2444 births.

INTRODUCTION: This study was conducted to evaluate and compare the incidence of birth defects in In-Vitro Fertilization-Intra Cytoplasmic Sperm Injection (IVF-ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF-ICSI pregnancies was compared with those from spontaneous conceptions in India. MATERIAL AND METHODS: This retrospective study included 2444 births resulting from IVF-ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3-year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth. RESULTS: The overall prevalence of birth defects in IVF-ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05). However, pregnancies resulting from autologous oocytes had a higher trend of gastrointestinal birth defects (20.5/10 000 births vs 0), though not statistically significant. The risk of cardiovascular birth defects resulting from IVF-ICSI pregnancies was much higher compared with the natural conceptions in India (32.7/10 000 vs 12.7/10 000 births; P = 0.03), whereas the risk of central nervous system malformations was much lower (8.1/10 000 vs 60.18/10 000 births; P = 0.005). CONCLUSIONS: Overall, there was no significant difference in birth defects resulting from IVF-ICSI with autologous or donor oocytes. The births resulting from IVF-ICSI pregnancies did not tend to have a higher rate of birth defects a compared with natural conceptions. The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF-ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF-ICSI. A study with larger number of sample size will give us better understanding of the prevalence of reported incidence in this study.

Assisted reproduction and risk of preterm birth in singletons by infertility diagnoses and treatment modalities: a population-based study.

PURPOSE: The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons. METHODS: Population-based assisted reproductive technology surveillance data for 2000-2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses. RESULTS: ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons. CONCLUSIONS: PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

Outcomes of IVF cycles coupled with PGS by aCGH of embryos from donor and autologous oocytes, transferred after vitrification to women of advanced maternal age.

It is well documented that aneuploidy rate in preimplantation embryos increases with the mother's age, and at the same time the number of oocytes diminishes. Consequently, for patients of advanced maternal age two options are available to overcome these limitations: use of oocytes from young donors, or use of own oocytes coupled with preimplantation genetic screening (PGS) for 24 chromosomes. However, it is not clear which strategy might be more effective. The aim of this retrospective study was to evaluate outcomes of IVF cycles coupled with transfer of vitrified embryos from donor or autologous oocytes, both with or without PGS. Our results demonstrate that while after PGS clinical pregnancy, twin pregnancy and spontaneous abortion rates are similar for embryos from donor and autologous oocytes, these rates are dramatically worse in all cycles without PGS. Therefore, PGS can be recommended as a screening method to all patients of advanced maternal age even when donor oocytes are used.

Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies.

Infertility, defined as the inability to conceive within 1 year of unprotected intercourse, affects an estimated 80 million individuals worldwide, or 10-15% of couples of reproductive age. Assisted reproductive technology includes all infertility treatments to achieve conception; in vitro fertilization is the process by which an oocyte is fertilized by semen outside the body; non-in vitro fertilization assisted reproductive technology treatments include ovulation induction, artificial insemination, and intrauterine insemination. Use of assisted reproductive technology has risen steadily in the United States during the past 2 decades due to several reasons, including childbearing at older maternal ages and increasing insurance coverage. The number of in vitro fertilization cycles in the United States has nearly doubled from 2000 through 2013 and currently 1.7% of all live births in the United States are the result of this technology. Since the birth of the first child from in vitro fertilization >35 years ago, >5 million babies have been born from in vitro fertilization, half within the past 6 years. It is estimated that 1% of singletons, 19% of twins, and 25% of triplet or higher multiples are due to in vitro fertilization, and 4%, 21%, and 52%, respectively, are due to non-in vitro fertilization assisted reproductive technology. Higher plurality at birth results in a >10-fold increase in the risks for prematurity and low birthweight in twins vs singletons (adjusted odds ratio, 11.84; 95% confidence interval, 10.56-13.27 and adjusted odds ratio, 10.68; 95% confidence interval, 9.45-12.08, respectively). The use of donor oocytes is associated with increased risks for pregnancy-induced hypertension (adjusted odds ratio, 1.43; 95% confidence interval, 1.14-1.78) and prematurity (adjusted odds ratio, 1.43; 95% confidence interval, 1.11-1.83). The use of thawed embryos is associated with higher risks for pregnancy-induced hypertension (adjusted odds ratio, 1.30; 95% confidence interval, 1.08-1.57) and large-for-gestation birthweight (adjusted odds ratio, 1.74; 95% confidence interval, 1.45-2.08). Among singletons, in vitro fertilization is associated with increased risk of severe maternal morbidity compared with fertile deliveries (vaginal: adjusted odds ratio, 2.27; 95% confidence interval, 1.78-2.88; cesarean: adjusted odds ratio, 1.67; 95% confidence interval, 1.40-1.98, respectively) and subfertile deliveries (vaginal: adjusted odds ratio, 1.97; 95% confidence interval, 1.30-3.00; cesarean: adjusted odds ratio, 1.75; 95% confidence interval, 1.30-2.35, respectively). Among twins, cesarean in vitro fertilization deliveries have significantly greater severe maternal morbidity compared to cesarean fertile deliveries (adjusted odds ratio, 1.48; 95% confidence interval, 1.14-1.93). Subfertility, with or without in vitro fertilization or non-in vitro fertilization infertility treatments to achieve a pregnancy, is associated with increased risks of adverse maternal and perinatal outcomes. The major risk from in vitro fertilization treatments of multiple births (and the associated excess of perinatal morbidity) has been reduced over time, with fewer and better-quality embryos being transferred.

Euploidy rates in donor egg cycles significantly differ between fertility centers.

Study question: Do external factors affect euploidy in egg donor cycles? Summary answer: The study demonstrates that during human assisted reproduction, embryonic chromosome abnormalities may be partly iatrogenic. What is known already: Chromosome abnormalities have been linked in the past to culture conditions such as temperature and Ph variations, as well as hormonal stimulation. Those reports were performed with older screening techniques (FISH), or ART methods no longer in use, and the subjects studied were not a homogeneous group. Study design, size, duration: A total of 1645 donor oocyte cycles and 13 282 blastocyst biopsies from 42 fertility clinics were included in this retrospective cohort study. Samples from donor cycles with PGS attempted between September 2011 and July 2015 were included. Participants/materials, setting, methods: PGS cycles from multiple fertility clinics referred to Reprogenetics (Livingston, NJ) that involved only oocyte donation were included in this study. Testing was performed by array comparative genomic hybridization (aCGH). Ploidy data were analyzed using Generalized Linear Mixed Models with logistic regression using a logit link function considering a number of variables that represent fixed and random effects. Main results and the role of chance: Euploidy rate was associated with the referring center and independent of almost all the parameters examined except donor age and testing technology. Average euploidy rate per center ranged from 39.5 to 82.5%. The mean expected rate of euploidy was 68.4%, but there are variations in this rate associated with the center effect. Limitations, reasons for caution: Data set does not include details of the donor selection process, donor race or ethnic origin, ovarian reserve or ovarian responsiveness. Due to the retrospective nature of the study, associations are apparent, however, causality cannot be established. Discrepancies in regard to completeness and homogeneity of data exist due to data collection from over 40 different clinics. Wider implications of the findings: This is the first study to show a strong association between center-specific ART treatment practices and the incidence of chromosome abnormality in human embryos, although the meiotic or mitotic origin of these abnormalities could not be determined using these technologies. Given the widespread applications of ART in both subfertile and fertile populations, our findings should be of interest to the medical community in general as well as the ART community in particular. Study funding/competing interest(s): No external funds were used for this study. S. Munne is a founding principle of Reprogenetics/current employee of Cooper Genomics. M Alikani's spouse is a founding principle of Reprogenetics/current consultant for Cooper Genomics. The remaining authors have no conflicts to declare.

The Human Oocyte Preservation Experience (HOPE) Registry: evaluation of cryopreservation techniques and oocyte source on outcomes.

BACKGROUND: This prospective, Phase IV, multicenter, observational registry of assisted reproductive technology clinics in the USA studied outcomes of first cycles using thawed/warmed cryopreserved (by slow-freezing/vitrification) oocytes (autologous or donor). METHODS: Patients were followed up through implantation, clinical pregnancy, and birth outcomes. The main outcome measure was live birth rate (LBR), defined as the ratio of live births to oocytes thawed/warmed minus the number of embryos cryopreserved for each cycle, averaged over all thawing cycles. Clinical pregnancy rate (CPR) was also evaluated, and was defined as the presence of a fetal sac with heart activity, as detected by ultrasound scan performed on Day 35-42 after embryo transfer. RESULTS: A total of 16 centers enrolled 204 patients; data from 193 patients were available for analyses. For donor oocytes, in the slow-freezing (n = 40) versus vitrification (n = 94) groups, respectively, CPR and LBR were significantly different: 32.4% versus 62.6%, and 25.0% versus 52.1%; outcomes from Day 3 transfers did not differ significantly. For vitrified oocytes, in the autologous (n = 46) versus donor (n = 94) group, respectively, CPR and LBR were significantly different: 30.0% versus 62.6% and 17.4% versus 52.1%. This was largely due to a significant difference in CPR with Day 5/6 transfers. CONCLUSIONS: In two subgroup data analyses, in women who received cryopreserved oocytes from donors, CPR and LBR were significantly higher in cycles using oocytes cryopreserved via vitrification versus slow-freezing, reflecting differences in methodologies and more Day 5/6 transfers; in women who received vitrified oocytes, CPR and LBR were significantly higher in cycles using donor versus autologous oocytes with Day 5/6 transfers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00699400 . Registered June 13, 2008.

Thermal and clinical performance of a closed device designed for human oocyte vitrification based on the optimization of the warming rate.

Although it was qualitatively pointed out by Fahy et al. (1984), the key role of the warming rates in non-equillibrium vitrification has only recently been quantitatively established for murine oocytes by Mazur and Seki (2011). In this work we study the performance of a closed vitrification device designed under the new paradigm, for the vitrification of human oocytes. The vitrification carrier consists of a main straw in which a specifically designed capillary is mounted and where the oocytes are loaded by aspiration. It can be hermetically sealed before immersion in liquid nitrogen for vitrification, and it is warmed in a sterile water bath at 37 °C. Measured warming rates achieved with this design were of 600.000 ºC/min for a standard DMEM solution and 200.000 ºC/min with the vitrification solution for human oocytes. A cohort of 143 donor MII sibling human oocytes was split into two groups: control (fresh) and vitrified with SafeSpeed device. Similar results were found in both groups: survival (97.1%), fertilization after ICSI (74.7% in control vs. 77.3% in vitrified) and good quality embryos at day three (54.3% in control vs. 58.1% in vitrified) were settled as performance indicators. The pregnancy rate was 3/6 (50%) for the control, 2/3 (66%) for vitrified and 4/5 (80%) for mixed transfers.