Clinical outcomes of single blastocyst transfer with machine learning guided noninvasive chromosome screening grading system in infertile patients.

BACKGROUND: Prospective observational studies have demonstrated that the machine learning (ML) -guided noninvasive chromosome screening (NICS) grading system, which we called the noninvasive chromosome screening-artificial intelligence (NICS-AI) grading system, can be used embryo selection. The current prospective interventional clinical study was conducted to investigate whether this NICS-AI grading system can be used as a powerful tool for embryo selection. METHODS: Patients who visited our centre between October 2018 and December 2021 were recruited. Grade A and B embryos with a high probability of euploidy were transferred in the NICS group. The patients in the control group selected the embryos according to the traditional morphological grading. Finally, 90 patients in the NICS group and 161 patients in the control group were compared statistically for their clinical outcomes. RESULTS: In the NICS group, the clinical pregnancy rate (70.0% vs. 54.0%, p < 0.001), the ongoing pregnancy rate (58.9% vs. 44.7%, p = 0.001), and the live birth rate (56.7% vs. 42.9%, p = 0.001) were significantly higher than those of the control group. When the female was ≥ 35 years old, the clinical pregnancy rate (67.7% vs. 32.1%, p < 0.001), ongoing pregnancy rate (56.5% vs. 25.0%, p = 0.001), and live birth rate (54.8% vs. 25.0%, p = 0.001) in the NICS group were significantly higher than those of the control group. Regardless of whether the patients had a previous record of early spontaneous abortion or not, the live birth rate of the NICS group was higher than that of the control group (61.0% vs. 46.9%; 57.9% vs. 34.8%; 33.3% vs. 0%) but the differences were not statistically significant. CONCLUSIONS: NICS-AI was able to improve embryo utilisation rate, and the live birth rate, especially for those ≥ 35 years old, with transfer of Grade A embryos being preferred, followed by Grade B embryos. NICS-AI can be used as an effective tool for embryo selection in the future.

Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives.

PURPOSE: We explored and compared perspectives of reproductive endocrinology and infertility specialists (REIs) and in vitro fertilization (IVF) patients regarding polygenic embryo screening (PES), a new type of preimplantation screening that estimates the genetic chances of developing polygenic conditions and traits in the future. METHODS: Qualitative thematic analysis of semi-structured interviews with US-based REIs and IVF patients. RESULTS: Clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more frequently than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer PES to patients or were willing to do so only under certain circumstances, while many patients expressed interest in PES. Both stakeholder groups envisioned multiple potential benefits or uses of PES and raised multiple potential, interrelated concerns about PES. CONCLUSION: A gap exists between clinician and patient attitudes toward PES; clinicians generally maintained reservations about such screening and patients indicated interest in it. Clinicians and patients sometimes imagined using PES to prepare for the birth of a predisposed or "affected" individual-a rationale that is often associated with prenatal testing. Many clinicians and patients held different attitudes depending on what is specifically screened, despite the sometimes blurry distinction between conditions and traits. Considerations raised by clinicians and patients may help guide professional societies in developing guidelines to navigate the uncertain terrain of PES.

Predictors of success after in vitro fertilization.

The last few decades have witnessed a rise in the global uptake of in vitro fertilization (IVF) treatment. To ensure optimal use of this technology, it is important for patients and clinicians to have access to tools that can provide accurate estimates of treatment success and understand the contribution of key clinical and laboratory parameters that influence the chance of conception after IVF treatment. The focus of this review was to identify key predictors of IVF treatment success and assess their impact in terms of live birth rates. We have identified 11 predictors that consistently feature in currently available prediction models, including age, duration of infertility, ethnicity, body mass index, antral follicle count, previous pregnancy history, cause of infertility, sperm parameters, number of oocytes collected, morphology of transferred embryos, and day of embryo transfer.

Planned oocyte cryopreservation to preserve future reproductive potential: an Ethics Committee opinion.

Planned oocyte cryopreservation is an ethically permissible procedure that may help individuals avoid future infertility. Because planned oocyte cryopreservation is new and evolving, it is essential that those considering using it be informed about the uncertainties regarding its efficacy and long-term effects. This replaces the document of the same name, last published in 2017.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Intravaginal exposure to seminal plasma after ovum pick-up does not increase live birth rates after in vitro fertilization or intracytoplasmic sperm injection treatment: a double-blind, placebo-controlled randomized trial.

OBJECTIVE: To detect whether intravaginal exposure to prepared seminal plasma led to an absolute increase in live birth rate (LBR) after in vitro fertilization (IVF) by 10% compared with placebo. It has been suggested that intravaginal deposition of seminal plasma after ovum pick-up (OPU) for IVF treatment, increases pregnancy and LBRs. DESIGN: Double-blind, placebo-controlled prospective study. An outcome assessment was made before the type of intervention was unblinded. The outcome data were analyzed according to an intention-to-treat protocol. SETTING: University Hospital. PATIENTS: Couples scheduled for an IVF treatment cycle: in total, 792 couples (393 in the seminal plasma group and 399 in the control group) were recruited over a 5-year period of inclusion in a single-center setting. INTERVENTION: On the day of OPU, the couples were randomized into groups receiving either vaginal deposition of prepared seminal plasma from the partner or saline. Both participants and the physician were blind to the grouping. MAIN OUTCOME MEASURES: The primary outcome was a live birth (LB). The secondary outcomes were a positive pregnancy test, defined as human chorionic gonadotropin identified in urine 3 weeks after OPU , and clinical pregnancy, defined as an intrauterine viable pregnancy assessed using transvaginal sonography after 5-7 weeks. RESULTS: In the index group, 35.4% had a positive pregnancy test (relative risk [RR],0.93; 95% confidence interval {CI} 0.78-1.10), 28.8% had a clinical pregnancy (RR 1.00, 95% CI 0.97-1.03), and 26.5% had a LB (RR 0.86; 95% CI 0.70-1.07), adjusted for day of transfer, female age, and number of fertilized oocytes. Corresponding rates in the control group were 37.3%, 33.6%, and 29.8%. No statistically significant differences regarding outcomes between the two intervention groups were found. CONCLUSION: Prepared seminal plasma applied in the vagina directly after OPU did not increase the rates of LB or clinical pregnancies. The importance of immunological factors to allow the implantation of an embryo is not questioned, but no improvement in the LBRs in IVF treatment by introducing the male partner's prepared seminal plasma after OPU could be found. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, ID NCT02716753. Registration date 17 March, 2016, first enrollment November, 2016, completed March, 2023.

The effect of laser-assisted hatching on vitrified/warmed blastocysts: the ALADDIN randomized controlled trial.

OBJECTIVE: To evaluate whether laser-mediated assisted hatching (AH) performed on vitrified/warmed blastocysts before embryo transfer can improve live birth rate. DESIGN: The "pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN)" is a 2-center comparative study with a parallel randomized controlled design. SETTING: University hospital. PATIENTS: Participants were recruited between September 2018 and November 2021. They were aged 18-39 years, underwent nondonor in vitro fertilization cycles, and were scheduled for elective single embryo transfer with vitrified/warmed blastocysts. Those with uterine abnormalities, body mass index of >35 kg/m2, severe male factor infertility, or performing preimplantation genetic testing were excluded. INTERVENTION: Assisted hatching was performed using a 1,480 nm diode laser, removing approximately one-third of the zona pellucida with continuous 0.2 ms pulses applied from the 1-5 o'clock positions. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate. Secondary end points included clinical pregnancy, miscarriage, multiple pregnancies, preterm births, obstetric and neonatal complications, and congenital anomalies. RESULTS: Overall, 698 participants met the inclusion criteria and were randomized: 352 patients were assigned to the AH arm and 346 to the control arm. Of the participants, 105 (29.8%) and 101 (29.2%), respectively, achieved a live birth after treatment. The relative risk of live birth in patients with vitrified/warmed blastocysts treated with AH was 1.02 (95% confidence interval, 0.86-1.19). Exploratory subgroup analyses for women's age, recruiting centers, indications for in vitro fertilization, method of insemination, blastocyst quality, and days of blastocyst development failed to highlight any clinical situation that could benefit from AH in thawed blastocysts. CONCLUSION: In patients undergoing frozen embryo transfer with vitrified/warmed blastocysts, laser AH does not improve the live birth rate. Further studies are required to rule out milder but potentially interesting benefits in specific subgroups of patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03623659.

The impact of microfluidics sperm processing on blastocyst euploidy rates compared with density gradient centrifugation: a sibling oocyte double-blinded prospective randomized clinical trial.

OBJECTIVE: To compare the euploidy rates among blastocysts created from sibling oocytes injected with sperm and processed using microfluidics or density gradient centrifugation. DESIGN: Sibling oocyte randomized controlled trial. SETTING: Single university-affiliated infertility practice. PATIENTS: A total of 106 patients aged 18-42 years undergoing fresh in vitro fertilization treatment cycles with preimplantation genetic testing between January 2021 and April 2022 contributed 1,442 mature oocytes, which were injected with sperm and processed using microfluidics or density gradient centrifugation. INTERVENTION(S): The sperm sample is divided and processed using a microfluidics device and density gradient centrifugation for injection into sibling oocytes. MAIN OUTCOME MEASURE(S): The primary outcome was the embryo euploidy rate. Secondary outcomes included fertilization, high-quality blastulation, and ongoing pregnancy rates. RESULT(S): The blastocyst euploidy rate per mature oocyte was not significantly different in the study group compared with the control group (22.9% vs. 20.5%). The blastocyst euploidy rate per biopsied embryo was also similar between the 2 groups (53.0% vs. 45.7%). However, the fertilization rate per mature oocyte injected was found to be significantly higher in the study group compared with the control group (76.0% vs. 69.9%). The high-quality blastulation rate per mature oocyte injected was similar between the 2 groups, as was the total number of embryos frozen. There were no differences in the number of participants with no blastocysts for biopsy or the number of participants with no euploid embryos between the 2 groups. Among the male factor infertility and recurrent pregnancy loss subgroups, there were no differences in euploidy rates, fertilization rates, blastulation rates, or total numbers of blastocysts frozen, although the study was underpowered to detect these differences. Seventy-seven patients underwent frozen embryo transfer; there were no significant differences in pregnancy outcomes between the 2 groups. CONCLUSION(S): Microfluidics processing did not improve embryo euploidy rates compared with density gradient centrifugation in this sibling oocyte study, although fertilization rates were significantly higher. CLINICAL TRIAL REGISTRATION NUMBER: NCT04744025.

Prophecy, prediction, and prognosis - can we improve the advice we give on the chance of pregnancy and treatment options for infertility?

Giving patients an accurate prognosis of their chances of achieving pregnancy is difficult with our current knowledge and technology. We need new approaches and thinking to provide truthful information.