Netanella Miller

Purpose: The use of in vitro fertilization (IVF) has increased substantially, raising interest in the long-term health outcomes of women undergoing these treatments. Objective: To assess the association between conception through autologous IVF and the long-term incidence of chronic diseases, compared with two reference groups: women who conceived through medically unassisted conception (UC) and age-matched nulliparous women. Methods: This retrospective cohort study used electronic health records from a large health maintenance organization and included women who delivered before age 45 between 2000 and 2018. Three pairwise comparisons were performed: IVF mothers versus UC mothers, IVF mothers versus nulliparous women, and UC mothers versus nulliparous women. For the IVF versus UC comparison, each IVF mother was matched to a UC mother by age and parity at delivery. For comparisons with nulliparous women, controls were matched by age according to the mother’s age at first delivery. The delivery date served as the index date for follow-up. Primary outcomes were chronic diseases diagnosed after the index pregnancy and persisting for at least three years. Results: The study included 17,425 IVF mothers matched to 17,425 UC mothers, 10,358 IVF mothers matched to 10,358 nulliparous women, and 38,810 UC mothers matched to 38,810 nulliparous women. Compared with UC, IVF was associated with a higher risk of thyroid disease (HR 1.11, p < 0.05). Compared with nulliparous women, IVF mothers had higher risks of thyroid disease (HR 2.07), rheumatologic disease (HR 1.87), neurologic disease (HR 2.51), and psychiatric conditions (HR 1.34) (all p < 0.05). UC mothers also had higher risks of thyroid disease (HR 1.67), rheumatologic disease (HR 1.79), cardiology disease (HR 1.47), and psychiatric conditions (HR 1.47) compared with nulliparous women (all p < 0.05). Conclusions: Long-term health outcomes after autologous IVF were largely comparable to those after UC, except for a modestly increased risk of thyroid disease. Compared with nulliparous women, both IVF and UC mothers had higher risks of several chronic conditions, suggesting that pregnancy itself may contribute to long-term maternal health trajectories. Thyroid function monitoring may be considered for women who conceive through autologous IVF.

This study evaluated the clinical outcomes associated with quantitative phase microscopy (QPM), an advanced 3D morphological sperm analysis technique using a virtual, stained model developed in our facility that indicates whether the inspected sperm should be selected for intracytoplasmic sperm injection (ICSI). We prospectively compared the clinical outcomes of three groups of cycles: (1) one with the QPM assessment, (2) one with conventional ICSI, without using QPM in the same patient, and (3) one with conventional ICSI cycles of an historical cohort of patients who did not undergo QPM. The outcomes of cycles using QPM vs. intracytoplasmic morphologically selected sperm injection (IMSI) cycles were also compared. A total of 1243 cycles were included. Pregnancy and delivery rates were higher among the QPM group compared to the standard ICSI group (56.2% vs. 18.1%, p = 0.04 and 50% vs. 9%, respectively, p = 0.02). Pregnancy and delivery rates were also higher among the QPM group compared to the IMSI group (56.2% vs. 16.6%, p = 0.01 and 50% vs. 16.6%, respectively, p = 0.03). No pregnancy complications were recorded in the QPM group. We conclude that QPM is a safe, non-invasive sperm selection technique for ICSI, with the potential to improve clinical pregnancy and delivery rates for couples with male infertility.

Purpose Studies have shown mixed findings regarding the impact of stress on the success of fertility treatments. To the best of our knowledge, stress in the context of the workplace has not been investigated to date in relation to the success of fertility treatments. This research investigates the impact of work-related stress and emotional exhaustion experienced by both partners on in vitro fertilization (IVF) treatment outcomes. Methods We conducted a cross-sectional study that included 44 heterosexual couples (N = 88) in which both partners filled out the research questionnaire. The couples were recruited in a hospital IVF unit in the center of Israel. Results Women’s job-related stress and emotional exhaustion lowered their chances of achieving pregnancy when undergoing IVF treatments. Moreover, when partners’ emotional exhaustion was relatively low, the job-related stress of women did not affect pregnancy outcomes. Conclusion This is the first study to explore whether job-related stressors of both partners may have an impact on success rates of IVF treatments. We propose some practical implications as to how to eradicate their negative impact on IVF outcomes.

This retrospective study applied machine-learning models to predict treatment outcomes of women undergoing elective fertility preservation. Two-hundred-fifty women who underwent elective fertility preservation at a tertiary center, 2019–2022 were included. Primary outcome was the number of metaphase II oocytes retrieved. Outcome class was based on oocyte count (OC): Low (≤ 8), Medium (9–15) or High (≥ 16). Machine-learning models and statistical regression were used to predict outcome class, first based on pre-treatment parameters, and then using post-treatment data from ovulation-triggering day. OC was 136 Low, 80 Medium, and 34 High. Random Forest Classifier (RFC) was the most accurate model (pre-treatment receiver operating characteristic (ROC) area under the curve (AUC) was 77%, and post-treatment ROC AUC was 87%), followed by XGBoost Classifier (pre-treatment ROC AUC 74%, post-treatment ROC AUC 86%). The most important pre-treatment parameters for RFC were basal FSH (22.6%), basal LH (19.1%), AFC (18.2%), and basal estradiol (15.6%). Post-treatment parameters were estradiol levels on trigger-day (17.7%), basal FSH (11%), basal LH (9%), and AFC (8%). Machine-learning models trained with clinical data appear to predict fertility preservation treatment outcomes with relatively high accuracy.

Background: Although there are some data regarding the COVID-19 vaccine and in in vitro fertilization (IVF) treatments, its potential impact in terms of serum immunoglobulin G (IgG) levels has not been evaluated prospectively. This study aimed to assess the effect of COVID-19 vaccine and IgG levels on IVF outcomes. Methods: This observational, cohort study was conducted at a referral IVF unit. Couples undergoing IVF treatment during the COVID-19 vaccination period were recruited from March–April 2021. The study compared 38 women who had received the Pfizer mRNA COVID-19 vaccination to 10 women who had not and were not infected by the virus. We also compared pre- and post-vaccination IVF treatments for 24 women. The relation between serologic titers and IVF treatment outcomes was also assessed. Results: No significant difference was found between the vaccinated and unvaccinated/uninfected groups regarding the main outcome measures. However, there was a trend toward a higher pregnancy rate for the unvaccinated group (57% vs. 23%, p = 0.078) but no difference in delivery rate (p = 0.236), gestational week (p = 0.537) or birth rate (p = 0.671). Conclusion: We cautiously state that the COVID-19 mRNA vaccine does not affect fertility outcomes, including fertilization, pregnancy and delivery rates, obstetric outcomes, and semen parameters, regardless of measured IgG levels.

Purpose: To analyze the perinatal and maternal outcomes of women ranging in age from 40 to 45 years who gave birth after in vitro fertilization or oocyte donation, compared to spontaneous conception. Methods: This retrospective cohort study used electronic data from a national healthcare service from 2000 through 2019. Three groups were compared: spontaneous pregnancy (SC), in vitro fertilization (IVF) utilizing autologous oocytes, and pregnancies resulting from oocyte donation (OD). The primary study outcomes were preterm labor (PTL) before 37 weeks of gestation, and infants classified as small for gestational age (SGA). Results: The cohort included 26,379 SC, 2237 IVF pregnancies, and 300 OD pregnancies for women ages 40–45 years at delivery. Women with OD or IVF had a higher incidence of PTL < 37 weeks compared to women with SC (19.7% vs. 18% vs. 6.9%, p = 0.001), PTL < 34 (7% vs. 4.5% vs. 1.4%, p = 0.001), PTL < 32 (3.7 vs. 2.1 vs. 0.6, p = 0.001). A multivariable logistic regression for PTL < 37 weeks demonstrated that age (OR = 1.18) and hypertensive diseases (OR = 3.4) were statistically significant factors. The OD group had a lower rate of SGA compared to SC (1% vs. 4.3%, p = 0.001), while the IVF group had a higher rate of SGA compared to SC (9.1% vs. 4.3%, p = 0.001). Hypertensive diseases in pregnancy were significantly higher among the OD group and the IVF group compared to SP pregnancies (3.3% vs. 1%, p = 0.002; 2.3% vs. 1%, p = 0.001, respectively). Conclusions: Women ages 40–45 undergoing IVF or OD have a greater risk of PTL, possibly due to higher rates of hypertensive disorders of pregnancy.

This multi-center study evaluated a novel microscope system capable of quantitative phase microscopy (QPM) for label-free sperm-cell selection for intracytoplasmic sperm injection (ICSI). Seventy-three patients were enrolled in four in vitro fertilization (IVF) units, where senior embryologists were asked to select 11 apparently normal and 11 overtly abnormal sperm cells, in accordance with current clinical practice, using a micromanipulator and 60× bright field microscopy. Following sperm selection and imaging via QPM, the individual sperm cell was chemically stained per World Health Organization (WHO) 2021 protocols and imaged via bright field microscopy for subsequent manual measurements by embryologists who were blinded to the QPM measurements. A comparison of the two modalities resulted in mean differences of 0.18 µm (CI −0.442–0.808 µm, 95%, STD—0.32 µm) for head length, −0.26 µm (CI −0.86–0.33 µm, 95%, STD—0.29 µm) for head width, 0.17 (CI −0.12–0.478, 95%, STD—0.15) for length–width ratio and 5.7 for acrosome–head area ratio (CI −12.81–24.33, 95%, STD—9.6). The repeatability of the measurements was significantly higher in the QPM modality. Surprisingly, only 19% of the subjectively pre-selected normal cells were found to be normal according to the WHO2021 criteria. The measurements of cells imaged stain-free through QPM were found to be in good agreement with the measurements performed on the reference method of stained cells imaged through bright field microscopy. QPM is non-toxic and non-invasive and can improve the clinical effectiveness of ICSI by choosing sperm cells that meet the strict criteria of the WHO2021.

Background: This study investigated whether high physical activity affects ovarian reserve in normo-ovulatory, reproductive-age women. Methods: This prospective, observational study compared 31 professional female athletes, with 31 women who did not engage in physical activity. It was conducted 2017–2020 in a tertiary medical center. Normo-ovulatory, professional athletes, ages 20–35 years were recruited from The Wingate Institute—the Israeli National Institute for Sport Excellence. They had high International Physical Activity Questionnaire (IPAQ) scores. Non-physically active women, matched by age and body mass index, were recruited from hospital staff. Women were evaluated for ovarian reserve markers on day 2–5 of the menstrual cycle, including follicular stimulating hormone, antral follicle count, anti-Mullerian hormone and Inhibin B. Results: The average age of the high physical activity group was 29.9 ± 4.2 years and the nonactive group 31.6 ± 4.2 years (p = 0.062). Body mass index of both groups were similar (22.5 ± 5.0 vs. 21.4 ± 2.5, respectively; p = 0.1). No differences were observed with respect to follicle stimulating hormone (p = 0.12) and anti-Mullerian hormone (p = 0.16). A trend towards higher total antral follicle count in the high physical activity group vs. the non-active group (34.5 ± 12.9 vs. 28.1 ± 15.2, p = 0.08) and lower Inhibin B (68.1 ± 36.8 vs. 89.4 ± 46.1, p = 0.05). Menarche age correlated with anti-Mullerian hormone (r = 0.387, p = 0.003), as did total antral follicle count (r = 0.368, p = 0.004). IPAQ scores and basal follicle stimulating hormone levels were negatively correlated (r = − 0.292, p = 0.005). Conclusions: Athletic, normo-ovulatory women have ovarian reserves that are at least as good as those of the general population. As this is the first study examining this issue, it could cautiously reassure women engaged in high physical activity regarding ovarian reserve.