An artificial intelligence model correlated with morphological and genetic features of blastocyst quality improves ranking of viable embryos.

RESEARCH QUESTION: Can better methods be developed to evaluate the performance and characteristics of an artificial intelligence model for evaluating the likelihood of clinical pregnancy based on analysis of day-5 blastocyst-stage embryos, such that performance evaluation more closely reflects clinical use in IVF procedures, and correlations with known features of embryo quality are identified? DESIGN: De-identified images were provided retrospectively or collected prospectively by IVF clinics using the artificial intelligence model in clinical practice. A total of 9359 images were provided by 18 IVF clinics across six countries, from 4709 women who underwent IVF between 2011 and 2021. Main outcome measures included clinical pregnancy outcome (fetal heartbeat at first ultrasound scan), embryo morphology score, and/or pre-implantation genetic testing for aneuploidy (PGT-A) results. RESULTS: A positive linear correlation of artificial intelligence scores with pregnancy outcomes was found, and up to a 12.2% reduction in time to pregnancy (TTP) was observed when comparing the artificial intelligence model with standard morphological grading methods using a novel simulated cohort ranking method. Artificial intelligence scores were significantly correlated with known morphological features of embryo quality based on the Gardner score, and with previously unknown morphological features associated with embryo ploidy status, including chromosomal abnormalities indicative of severity when considering embryos for transfer during IVF. CONCLUSION: Improved methods for evaluating artificial intelligence for embryo selection were developed, and advantages of the artificial intelligence model over current grading approaches were highlighted, strongly supporting the use of the artificial intelligence model in a clinical setting.

Differences in pregnancy outcomes in donor egg frozen embryo transfer (FET) cycles following preimplantation genetic screening (PGS): a single center retrospective study.

PURPOSE: This study aims to test the hypothesis, in a single-center retrospective analysis, that live birth rates are significantly different when utilizing preimplantation genetic screening (PGS) compared to not utilizing PGS in frozen-thawed embryo transfers in our patients that use eggs from young, anonymous donors. The question therefore arises of whether PGS is an appropriate intervention for donor egg cycles. METHODS: Live birth rates per cycle and live birth rates per embryo transferred after 398 frozen embryo transfer (FET) cycles were examined from patients who elected to have PGS compared to those who did not. Blastocysts derived from donor eggs underwent trophectoderm biopsy and were tested for aneuploidy using array comparative genomic hybridization (aCGH) or next-generation sequencing (NGS), then vitrified for future use (test) or were vitrified untested (control). Embryos were subsequently warmed and transferred into a recipient or gestational carrier uterus. Data was analyzed separately for single embryo transfer (SET), double embryo transfer (DET), and for own recipient uterus and gestational carrier (GC) uterus recipients. RESULTS: Rates of implantation of embryos leading to a live birth were significantly higher in the PGS groups transferring two embryos (DET) compared to the no PGS group (GC, 72 vs. 56 %; own uterus, 60 vs. 36 %). The live birth implantation rate in the own uterus group for SET was higher in the PGS group compared to the control (58 vs. 36 %), and this almost reached significance but the live birth implantation rate for the SET GC group remained the same for both tested and untested embryos. Live births per cycle were nominally higher in the PGS GC DET and own uterus SET and DET groups compared to the non-PGS embryo transfers. These differences almost reached significance. The live birth rate per cycle in the SET GC group was almost identical. CONCLUSIONS: Significant differences were noted only for DET; however, benefits need to be balanced against risks associated with multiple pregnancies. Results observed for SET need to be confirmed on larger series and with randomized cohorts.

Validation of next-generation sequencing for comprehensive chromosome screening of embryos.

Massively parallel genome sequencing, also known as next-generation sequencing (NGS), is the latest approach for preimplantation genetic diagnosis. The purpose of this study was to determine whether NGS can accurately detect aneuploidy in human embryos. Low coverage genome sequencing was applied to trophectoderm biopsies of embryos at the blastocyst stage of development. Sensitivity and specificity of NGS was determined by comparison of results with a previously validated platform, array-comparative genomic hybridization (aCGH). In total, 156 samples (116 were blindly assessed) were tested: 40 samples were re-biopsies of blastocysts where the original biopsy specimen was previously tested for aCGH; four samples were re-biopsies of single blastomeres from embryos previously biopsied at the cleavage stage and tested using aCGH; 18 samples were single cells derived from well-characterized cell lines; 94 samples were whole-genome amplification products from embryo biopsies taken from previous preimplantation genetic screening cycles analysed using aCGH. Per embryo, NGS sensitivity was 100% (no false negatives), and 100% specificity (no false positives). Per chromosome, NGS concordance was 99.20%. With more improvement, NGS will allow the simultaneous diagnosis of single gene disorders and aneuploidy, and may have the potential to provide more detailed insight into other aspects of embryo viability.

Laparoscopic tubal reanastomosis using robotics: experience from a teaching institution.

PURPOSE: Tubal reanastomosis typically requires a laparotomy and in the past few years has been performed much less frequently due to the development and success of in vitro fertilization. Laparoscopic tubal anastomosis eliminates the need for laparotomy and can be performed in an out-patient setting. MATERIALS AND METHODS: From October 2003 to September 2004, five patients who had previous tubal sterilization and requested tubal reanastomosis underwent laparoscopic tubal reanastomosis with the use of the da Vinci surgical system (Intuitive Surgical, Mountain View, CA). RESULTS: Ten fallopian tubes were successfully reconstructed, as confirmed by chromopertubation at the end of the procedure. Patency was confirmed by hysterosalpingogram in seven out of eight tubes. The mean (+/- standard deviation) time of the procedure was 172 +/- 53 min. The mean time for docking the robotic arms to the patient was 62 +/- 16.8 min and the mean robotic time was 97 +/- 36 min. There were two live births, one ectopic pregnancy, and one biochemical pregnancy. The mean time to conception was 5.5 +/- 2 months. CONCLUSION: Laparoscopic microsurgical tubal reanastomosis after tubal sterilization can be performed using a remote-controlled robotic system. Systematization of the operative steps allowed for operative times that compare favorably with the time needed for open microsurgical techniques. Larger series are needed to standardize the procedure and confirm postoperative fecundity rates.

Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial.

OBJECTIVE: To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening. DESIGN: Randomized controlled trial. SETTING: Private assisted reproduction center. PATIENT(S): A total of 179 patients undergoing IVF treatment using preimplantation genetic screening. INTERVENTION(S): Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle. MAIN OUTCOME MEASURE(S): Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle. RESULT(S): Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group. CONCLUSION(S): Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos. CLINICAL TRIAL REGISTRATION NUMBER: NCT02000349.

Long-term corticosteroid replacement and bone mineral density in adult women with classical congenital adrenal hyperplasia.

CONTEXT: Concern has been raised regarding the potential impact of chronic glucocorticoid therapy on the bone mineral density (BMD) of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: The purpose of this investigation was to assess the impact of chronic glucocorticoid replacement in adult women with classical CAH. PATIENTS AND DESIGN: We used dual energy x-ray absorptiometry to evaluate lumbar spine and whole body BMD in 11 women with salt-losing (SL) CAH and 15 with the simple virilizing form. Physical characteristics and serum hormone concentrations were also measured. Results were compared with those of unaffected sisters of CAH patients (n = 9). MAIN OUTCOME MEASURE: BMD was the main outcome measure. RESULTS: Osteopenia was noted in 45% of SL CAH patients, 13% of patients with the simple virilizing form, and 11% of controls. Lumbar spine and whole body BMDs of CAH subjects were lower than those of controls (P < 0.05). Compared with CAH subjects with normal BMD, those with osteopenia had reduced serum levels of dehydroepiandrosterone sulfate and dehydroepiandrosterone. Adrenal androgen levels were particularly suppressed among postmenopausal women receiving glucocorticoid replacement. CONCLUSIONS: Adult women with classical CAH treated with long-term glucocorticoids are at risk for decreased BMD, especially those with the SL form. Oversuppression of adrenal androgens is associated with increased risk for bone loss in this population.

Effect of luteal-phase support on endometrial L-selectin ligand expression after recombinant follicle-stimulating hormone and ganirelix acetate for in vitro fertilization.

CONTEXT: The impact of different types of luteal phase support on endometrial receptivity after ovarian stimulation has not been investigated. OBJECTIVE: Our objective was to evaluate the impact of different luteal-phase support protocols on sex steroid levels and on endometrial expression of L-selectin ligand after ovarian hyperstimulation with a GnRH antagonist protocol. PATIENTS AND DESIGN: Seventeen oocyte donors who underwent ovarian stimulation with a recombinant FSH/ganirelix acetate protocol were randomized into three groups: group I had no luteal-phase support; group II had luteal support with micronized progesterone; and group III had luteal support with progesterone plus 17beta-estradiol. All donors had endometrial biopsies on the day of retrieval, and then 3, 5, and 10 d after retrieval. In addition, they had serum estradiol and progesterone measurements on d 3, 5, and 10. MAIN OUTCOME MEASURES: Endometrial L-selectin ligand expression was detected by immunohistochemical staining in the luminal and glandular epithelium. A histological score was used for the quantification of the immunostaining. Sex steroid levels were measured during the luteal phase. RESULTS: By d 10 after retrieval, there was a significant decrease in mean progesterone levels in group I compared with the other two groups that may reflect the expected demise of the corpus luteum. There was also a significant increase in the presence of L-selectin ligands in the luminal epithelium in group III. CONCLUSIONS: During controlled ovarian stimulation with a GnRH antagonist protocol, luteal-phase support with micronized progesterone and 17beta-estradiol seem to increase endometrial L-selectin ligand expression in the luminal endothelium.

Fertility patients' views about frozen embryo disposition: results of a multi-institutional U.S. survey.

OBJECTIVE: To describe fertility patients' preferences for disposition of cryopreserved embryos and determine factors important to these preferences. DESIGN: Cross-sectional survey conducted between June 2006 and July 2007. SETTING: Nine geographically diverse U.S. fertility clinics. PATIENT(S): 1020 fertility patients with cryopreserved embryos. INTERVENTION(S): Self-administered questionnaire. MAIN OUTCOME MEASURE(S): Likelihood of selecting each of five conventional embryo disposition options: store for reproduction, thaw and discard, donate to another couple, freeze indefinitely, and donate for research; likelihood of selecting each of two alternative options identified in previous research: placement of embryos in the woman's body at an infertile time, or a disposal ceremony; importance of each of 26 considerations to disposition decisions; and views on the embryo's moral status. RESULT(S): We found that 54% of respondents with cryopreserved embryos were very likely to use them for reproduction, 21% were very likely to donate for research, 7% or fewer were very likely to choose any other option. Respondents who ascribed high importance to concerns about the health or well-being of the embryo, fetus, or future child were more likely to thaw and discard embryos or freeze them indefinitely. CONCLUSION(S): Fertility patients frequently prefer disposition options that are not available to them or find the available options unacceptable. Restructuring and standardizing the informed consent process and ensuring availability of all disposition options may benefit patients, facilitate disposition decisions, and address problems of long-term storage.

Variations in L-selectin ligand expression in the luteal-phase endometrium after final oocyte maturation with human chorionic gonadotropin compared with a gonadotropin-releasing hormone agonist.

Final oocyte maturation was achieved by using hCG or two doses of leuprolide acetate in 16 oocyte donors after a GnRH antagonist protocol. Administration of hCG was associated with a statistical trend toward increased L-selectin ligand expression in the endometrium on postretrieval day 5, compared with the leuprolide acetate group.

Expression of L-selectin ligands in human endometrium during the implantation window after controlled ovarian stimulation for oocyte donation.

L-selectin ligands were detected in the epithelial endometrium throughout the implantation window, whereas the level of expression was significantly reduced in the donor versus control group on cycle day 19 (P<.05) in the luminal epithelium and during cycle days 19-24 in the glandular epithelium. Controlled ovarian stimulation, using the antagonist protocol in this study, is associated with a reduction of L-selectin ligand expression during the implantation window which may adversely affect the endometrial environment.

The association between menopausal symptoms and quality of life in midlife women.

This cross-sectional study examined 1,096 midlife women, associating menopausal symptoms, including hot flashes, vaginal dryness, sore joints, incontinence, irritability, mood changes, and headache, with quality of life (QOL), as measured using Cantril's Ladder of Life. The results showed that low QOL may be significantly associated with feeling tense and mood changes, but not the other selected symptoms.

The social implications of embryo cryopreservation.

OBJECTIVE: To summarize the existing literature regarding the social implications of embryo cryopreservation and outline areas in need of further study. RESULT(S): The potential social impact of oocyte cryopreservation has not been investigated. Embryo cryopreservation has been increasingly used to improve the cost-effectiveness of in vitro fertilization (IVF) and expand the options available to infertile couples, yet its widespread adoption has occurred more rapidly than our ability to study the social consequences for the couples and health professionals involved. For maintaining cryopreserved embryos, the existing literature is fragmented and incompletely explores the effects on an infertile couple's psychosocial health and personal relationships, their family planning strategies, or their preferences for the disposition of the embryos. Managing unclaimed embryos continues to create challenges for assisted reproduction professionals. CONCLUSION(S): We currently lack a thorough understanding of the numerous social implications of cryopreservation. Major areas for future research include the impact of stored embryos on couples' fertility intentions and psychosocial health, factors that affect couples' decisions about embryo disposition, strategies to minimize unclaimed embryos, and the consequences of oocyte/ovarian cryopreservation.

Women with ovulatory dysfunction undergoing ovarian stimulation with clomiphene citrate for intrauterine insemination may benefit from administration of human chorionic gonadotropin.

OBJECTIVE: To investigate factors that may affect pregnancy outcome following ovarian stimulation with clomiphene citrate (CC) combined with intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: University teaching hospital. PATIENT(S): Three hundred and twenty women who underwent 691 ovarian stimulation cycles with CC for IUI. INTERVENTION(S): Ovarian stimulation with CC followed by a single IUI either 24 hours after a spontaneous serum LH surge (>25 mIU/mL) or 36 hours after intramuscular human chorionic gonadotropin (hCG) administration (10,000 IU) when the largest follicle had reached a diameter of 17 mm. MAIN OUTCOME MEASURE(S): Clinical pregnancies. RESULT(S): Women with ovulatory dysfunction who received hCG had significantly higher pregnancy rates (24.6%) compared with women with other types of infertility. There were no differences in pregnancy rates between the LH surge group and the hCG group (14.3% vs 12.4%). A spontaneous LH surge was noted in a variety of follicular sizes (14 to 35 mm). There was no correlation for age, body mass index, follicular diameter, number of mature follicles, other sperm characteristics, and pregnancy outcome in either group. CONCLUSION(S): After ovarian stimulation with CC, IUI is equally effective 24 hours after a spontaneous LH surge or 36 hours after administration of hCG. Spontaneous LH surges were observed at a variety of follicular sizes with comparable pregnancy rates. In women with ovulatory dysfunction, hCG administration before insemination may be beneficial.

Effect of ejaculatory abstinence period on the pregnancy rate after intrauterine insemination.

OBJECTIVE: To determine the optimal interval of ejaculatory abstinence for couples undergoing IUI. DESIGN: Retrospective analysis. SETTING: Reproductive endocrinology and infertility center. PATIENT(S): Infertile couples undergoing ovulation induction and IUI with partner's semen. INTERVENTION(S): Ovulation induction with clomiphene citrate and a single IUI procedure per cycle. MAIN OUTCOME MEASURES(S): Clinical pregnancy rates as a function of abstinence intervals. RESULT(S): Four hundred seventeen women underwent 929 cycles from June 1999 to October 2002 for a median of 4 IUI attempts per couple. The median ejaculatory abstinence interval was 4 days (range 0-30) with an overall pregnancy rate of 12% per cycle. Abstinence correlated positively with inseminate sperm count but negatively with motility. Variations in inseminate parameters did not correlate with pregnancy rates. However, abstinence intervals significantly affected pregnancy rates. The highest pregnancy rate was observed with an abstinence interval of 3 days or less (14%) and the lowest pregnancy rate seen with an abstinence interval of 10 days or more (3%). CONCLUSION(S): An abstinence interval of 3 days or less was associated with higher pregnancy rates following IUI. Prolonged abstinence decreases pregnancy rates, independent of other sperm parameters, perhaps as a result of sperm senescence and functional damage not readily identified by standard semen analysis. Abstinence intervals should be controlled for in studies examining pregnancy outcome in assisted reproduction.