Impact of inactivated SARS-CoV-2 vaccination on blastocyst euploidy status: a prospective cohort study of patients undergoing preimplantation genetic testing for aneuploidy in China.

A total of 390 patients were enrolled and 32 patients were excluded. A flowchart of the recruitment process is shown in Fig.  1 . Fig. 1 Flowchart of patient enrollment Flowchart of patient enrollment The female age, BMI, duration and type of infertility, AFC, serum level of basal sex hormones, male age, sperm parameters and semen diagnosis, indications for PGT-A were not significantly different between the two groups ( P  > 0.05). In the vaccinated group, the proportion of vaccinated male was significantly higher than that in the unvaccinated group ( P  < 0.05) (Table  1 ). Table 1 Basal characteristics of the study population Variables Vaccinated group ( n  = 214) Unvaccinated group ( n  = 176) Z/X 2 P Female age (years) a 32.00 (28.75, 36.00) 32.00 (29.00, 36.00) -0.953 0.340 BMI (kg/m 2 ) a 21.50 (19.77, 23.64) 21.86 (20.02, 23.44) -1.007 0.314 Duration of infertility (years) a 1.00 (0.00, 3.00) 2.00 (0.43, 2.75) -0.084 0.933 Type of infertility, n (%) b 0.855 0.355  Primary 47 (21.96%) 32 (18.18%)  Secondary 167 (78.04%) 144 (81.82%) AFC a 14.00 (10.00, 20.00) 14.00 (9.00, 20.00) -0.099 0.921 AMH (ng/mL) a 2.80 (1.66, 4.46) 2.84 (1.63, 4.41) -0.316 0.752 basal FSH (IU/mL) a 6.73 (5.72, 8.29) 7.09 (5.88, 8.45) -0.634 0.526 basal LH (IU/mL) a 4.63 (3.79, 6.60) 4.56 (3.04, 5.92) -1.810 0.070 basal E 2 (pg/mL) a 31.73 (25.95, 42.98) 34.66 (26.12, 47.68) -1.343 0.179 basal P (ng/mL) a 0.44 (0.30, 0.58) 0.40 (0.30, 0.54) -1.161 0.246 TT (ng/mL) a 0.23 (0.15, 0.34) 0.22 (0.14, 0.38) -0.355 0.722 PRL (µIU/mL) a 309.00 (237.21, 418.72) 298.80 (220.24, 433.30) -0.425 0.671 Male age (years) a 34.00 (31.00, 37.00) 34.00 (31.00, 38.00) -0.528 0.598 Male vaccination status, n (%) b 190.313 < 0.001  Unvaccinated 7 (3.27%) 122 (69.32%)  Vaccinated 207 (96.73%) 54 (30.68%) Sperm parameters a  Total count (millions) 180.65 (104.83, 280.55) 176.00 (115.20, 281.75) -0.310 0.757  Sperm concentration (millions/mL) 62.50 (39.25, 89.75) 61.50 (35.50, 94.50) -0.402 0.688  Viability (%) 85.00 (80.00, 87.00) 85.00 (80.00, 86.00) -1.216 0.224  Progressive motility (%) 50.00 (38.00, 60.00) 51.00 (39.50, 62.00) -0.594 0.552  Rate of normal morphology (%) 4.50 (2.50, 6.00) 4.12 (2.24, 6.30) -0.664 0.507 Male semen diagnosis, n (%) b  Normospermic 113 (52.80%) 78 (44.32%) 2.783 0.095  Oligozoospermia 17 (7.94%) 21 (11.93%) 1.746 0.186  Severe oligozoospermia 5 (2.33%) 10 (5.68%) 2.923 0.087  Asthenozoospermia 31 (14.49%) 22 (12.50%) 0.324 0.657  Oligoasthenozoospermia 8 (3.74%) 4 (2.27%) 0.696 0.404  Teratozoospermia 77 (35.98%) 74 (42.05%) 1.497 0.221 Indications for PGT-A b 0.284 0.868  Recurrent implantation failure 32 (14.95%) 23 (13.07%)  Recurrent pregnancy loss 158 (73.83%) 133 (75.57%)  Advanced maternal age 24 (11.21%) 20 (11.36%) a Mann-Whitney U test b Chi-square test Basal characteristics of the study population a Mann-Whitney U test b Chi-square test The proportion of different OS protocols, rFSH dose and duration, serum levels of E 2 and P on the trigger day, number of oocytes retrieved were not significantly different among both groups ( P  > 0.05) (Table  2 ). No moderated or severe OHSS has occurred in all patients. Table 2 Characteristics of ovarian stimulation Variables Vaccinated ( n  = 214) Unvaccinated ( n  = 176) Z/X 2 P OS protocol ( n , %) b 2.652 0.103  GnRH-A 115 (53.74%) 109 (61.93%)  PPOS 99 (46.26%) 67 (38.07%) rFSH dose (IU) a 2587.50 (2175.00, 3000.00) 2700.00 (2250.00, 3075.00) -1.181 0.238 rFSH duration (day) a 9.00 (9.00, 10.00) 10.00 (9.00, 11.00) -1.927 0.054 Serum E 2 on the trigger day (pg/mL) a 2737.00 (1812.81, 4288.19) 2641.00 (1568.00, 3956.00) -1.010 0.313 Serum P on the trigger day (ng/mL) a 1.21 (0.79, 1.78) 1.10 (0.70, 1.56) -1.953 0.051 Oocytes retrieved (n) a 11.00 (8.00, 17.00) 11.00 (7.00, 17.00) -1.077 0.281 a Mann-Whitney U test b Chi-square test Characteristics of ovarian stimulation a Mann-Whitney U test b Chi-square test In the vaccinated group, 42 patients had canceled the PGT-A (1 cancelled oocyte retrieval, 2 failed oocyte retrieval, 1 failed cleavage, and 38 failed usable blastocyst formation). In the unvaccinated group, 31 patients had canceled the PGT-A (2 failed fertilization, 6 failed cleavage and 23 failed usable blastocyst formation). As the result, 172 patients from the vaccinated group and 145 patients from the unvaccinated group had undergone PGT-A (Fig.  1 ). The rates of MII oocyte, 2PN, cleavage embryo, high-quality cleavage embryo, usable blastocyst and high-quality blastocyst were not significantly different between the two groups ( P  > 0.05). The euploidy, aneuploidy and mosaicism rate per blastocyst undergone PGT-A, the proportions of cycles with euploid blastocyst in PGT-A cycle and in OS cycle were not significantly different between the two groups ( P  > 0.05) (Table  3 ). Table 3 Outcomes of oocytes and embryos Variables Vaccinated ( n  = 214) Unvaccinated ( n  = 176) X 2 P MII oocyte rate (%) a 80.51% (2255/2801) 81.20% (1762/2170) 0.377 0.539 2PN rate (%) a 68.87% (1553/2255) 70.26% (1238/1762) 0.904 0.342 Cleavage embryo rate (%) a 92.60% (1438/1553) 91.60% (1134/1238) 0.944 0.331 High-quality cleavage embryo rate (%) a 28.78% (447/1553) 30.94% (383/1238) 1.530 0.216 Usable blastocyst rate (%) a 39.41% (612/1553) 39.18% (485/1238) 0.015 0.901 High-quality blastocyst rate (%) a 9.14% (142/1553) 10.58% (131/1238) 1.614 0.204 Euploidy status per blastocyst undergone PGT-A a  Euploidy rate (%) 51.14% (313/612) 55.88% (271/485) 2.434 0.119  Aneuploidy rate (%) 30.23% (185/612) 25.77% (125/485) 2.650 0.104  Mosaicism rate (%) 18.63% (114/612) 18.35% (89/485) 0.014 0.907 Proportion of cycles with euploidy blastocyst a  In PGT-A cycle (%) 75.58% (130/172) 82.76% (120/145) 2.431 0.119  In OS cycle (%) 60.75% (130/214) 68.18% (120/176) 2.319 0.128 a Chi-square test Outcomes of oocytes and embryos a Chi-square test The endometrial thickness on the FET day, proportion of cycles with high-quality blastocyst transferred, rates of implantation, clinical pregnancy, early miscarriage, ongoing pregnancy, live birth, gestational age at delivery, birth length and weight of infants were not significantly different between the two groups ( P  > 0.05) (Table  4 ). No late miscarriage and multiple pregnancy had occurred. One ectopic pregnancy was occurred in unvaccinated group. In the vaccinated group, 1 woman had pregnancy-induced hypertension (PIH) and 1 woman had gestational diabetes mellitus (GDM). In unvaccinated group, 2 women had GDM. The mean gestational age at delivery was 38 weeks (range, 29 ~ 41weeks). The mean birth weight was 3218 g (range, 1150 ~ 4300 gram) and birth height was 49 cm (range, 43 ~ 53 cm). None of the 113 live-born infants (58 boys and 55 girls) was found to have a birth defects (Table  4 ). Table 4 Outcomes of the first freeze-thawed embryo transfer Variables Vaccinated ( n  = 103) Unvaccinated ( n  = 100) Z/X 2 P Endometrial thickness (mm) a 8.00 (7.50, 10.00) 8.00 (7.50, 10.00) -0.148 0.882 Proportion of cycles with high-quality blastocyst transferred (%) b 39.81% (41/103) 36.00% (36/100) 0.312 0.576 Implantation rate (%) b 59.22% (61/103) 66.00% (66/100) 0.995 0.319 Clinical pregnancy rate (%) b 59.22% (61/103) 66.00% (66/100) 0.995 0.319 Early miscarriage rate (%) b 11.48% (7/61) 9.09% (6/66) 0.196 0.658 Ongoing pregnancy rate (%) b 52.43% (54/103) 59.00% (59/100) 0.888 0.346 Live birth rate (%) b 52.43% (54/103) 59.00% (59/100) 0.888 0.346 Gestational age at delivery (week) a 38.00 (38.00, 39.00) 38.00 (37.00, 39.00) -0.334 0.731 Birth length (cm) a 50.00 (48.75, 50.00) 50.00 (48.00, 50.00) -0.577 0.564 Birth weight (gram) a 3300.00 (3065.00, 3505.00) 3200.00 (3050.00, 3500.00) -0.564 0.573 a Mann-Whitney U test b Chi-square test Outcomes of the first freeze-thawed embryo transfer a Mann-Whitney U test b Chi-square test

From January 2022 to February 2023, patients undergoing the first cycle of PGT-A treatment at the Reproductive Medicine Center of Sichuan Provincial Women’s and Children’s Hospital were prospectively enrolled. The reasons for PGT-A have included advanced maternal age, recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF). The exclusion criteria have included: (1) a history of SARS-CoV-2 infection; (2) inaccurate information of vaccination; (3) congenital uterine malformation, submucosal or intramural uterine fibroids, endometriosis and adenomyosis; (4) fertilization with donor’s sperm or oocyte; (5) husband’s sperm by testicular aspiration; (6) abnormal karyotype. The patients were divided into two groups based on their history of vaccination before the ovarian stimulation (OS). The full course of inactivated SARS-CoV-2 vaccination in China has consisted of three doses, with the second dose inoculated one month later after the first dose, and the third(booster) dose inoculated six months later after the second dose. The patients from the vaccinated group were inoculated with three doses of inactivated SARS-CoV-2 vaccine at least one month before the OS. Prior to the OS, the information of vaccination (date of inoculation, type and manufacturer of the vaccine) were recorded by a nurse via Tianfu Tong (an application program of Sichuan Health Database) installed on the mobile phone. All patients were routinely detected for nucleic acid to exclude SARS-CoV-2 infection before the OS. The antral follicle count (AFC), body mass index (BMI), and serum levels of follicular stimulation hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), progesterone (P), total testosterone (TT), prolactin and anti-Müllerian hormone (AMH) were measured as described previously [ 24 ]. All semen analyses were carried out in accordance with the Fifth Edition of WHO Laboratory Manual for Examination and Processing (2010). The gonadotropin-releasing hormone antagonist (GnRH-A) protocol or progestin-primed ovarian stimulation (PPOS) protocol was conducted for OS. All patients had received daily injection of 225 ~ 300 IU of recombinant FSH (rFSH, Gonal-F, Merck-Serono KGaA., Darmstadt, Germany; Jinsai Heng, Jinsai Pharmaceuticals, China; Puregon ® , Merck Sharp & Dohme, USA) from day 2 ~ 3 of the menstrual cycle till the trigger day. The dose of rFSH was adjusted according to the follicular development and serum level of E 2 . In GnRH-A protocol, when the diameter of dominant follicle reached 14 mm or serum level of LH ≥ 10 mIU/mL, 0.25 mg GnRH-A (Ganirelix, Ocalon, USA) was daily injected subcutaneously till the trigger day. With the PPOS protocol, 10 mg medroxyprogesterone acetate (MPA) (Zhejiang Xianju, China) was taken orally from day 2 ~ 3 of the menstrual cycle till the trigger day, which was accompanied with rFSH. With both OS protocols, when the diameter of at least 1 or 2 follicles have reached 18 mm, 250 µg of recombinant HCG (rHCG, Merck-Sheranova, Germany) was injected as the trigger, and the oocytes were retrieved under transvaginal ultrasound guidance after 36.5 h. Ovarian hyper-stimulation syndrome (OHSS) was diagnosed and graded according to Navot et al. [ 25 ]. Following oocytes retrieval, those with the first polar body discharged from perivitelline gap was considered as mature (metaphase II, MII) oocytes. The MII oocytes were fertilized through intracytoplasmic sperm injection (ICSI). The presence of two pronuclear zygotes (2PN) in the cytoplasm 16 ~ 18 h after the fertilization was considered a normal fertilized oocyte. The embryo was cultured to cleavage and blastocyst stage in sequential G1-plus/G2-plus medium (Vitrolife, Sweden) at 37 °C in a culture environment containing 6.0% CO 2 and 5% O2. Day 3 cleavage embryo was scored according to the number of blastomeres and the degree of fragmentation, the high-quality embryo was categorised as grade Ⅰ or Ⅱ [ 26 ]. On day 5 or 6, morphological scoring was carried out based on the Gardner and Schoolcraft’s system [ 26 ]. Blastocysts with a grade over 4CC were considered as usable and biopsied, and those graded over 4BB were considered as high-quality ones. The trophectoderm of usable blastocysts was biopsied with a micro-laser pulse combined with mechanical blunt dissection, and 5 ~ 7 trophectoderm cells were obtained (Sunlight, USA). The trophectoderm cells were washed 3 times in phosphate buffer saline, transferred into polymerase chain reaction (PCR) tubes containing protective fluid, and stored at -80℃ until detection. Thereafter, the DNA of the trophectoderm cells had undergone a series of multiple annealing and looping-based amplification cycles using a commercially made single-cell whole-genome amplification (WGA) kit (Yikon Medical Technology Co., Ltd., China) Following the WGA, the DNA samples were diluted, enzymatically fragmented, and ligated with sequencing adaptors. The prepared samples had undergong PCR amplification and were subsequently purified to ensure the integrity. The concentration of the purified DNA was quantified with Invitrogen Qubit 4 (Thermo Scientific, USA) prior to the sequencing. High-throughput next-generation sequencing was carried out on a DA8600 sequencing platform (Yikon Medical Technology Co., Ltd, China). According to the instructions of PGT-A test kit used, those with  70% as Aneuploid. A multidisciplinary team consisted of geneticist, clinician, and embryologist has ensured transfer eligibility and priority order through integrated analysis of ploidy status and morphological grading to determine the suitability for the transferring procedure for each blastocyst. Euploid blastocysts with the highest morphological grades were preferentially transferred. Biopsied blastocysts were all cryopreserved by vitrification. Vitrification was performed using a two-step protocol with commercial vitrification kits (Kitazato Biotech Co., Ltd., Japan). Briefly, blastocysts were first subjected to laser-assisted collapse, then equilibrated in the equilibration solution for 8 ~ 12 min, followed by exposure to the vitrification solution for no longer than 60 s, both at room temperature. The embryos were subsequently loaded onto a Cryotop device (Guangzhou Hehong Biotech Co., Ltd, China) in a minimal volume (< 1 µL) and immediately plunged into liquid nitrogen. The endometrium was prepared by hormone replacement therapy (HRT) in the freeze-thawed embryo transfer (FET) cycle at least two months later. The patients were given orally 6 mg/day estradiol valerate (Progynova, Bayer, Germany) from days 2 ~ 3 of menstruation. At least 12 days later, when the endometrial thickness was ≥ 8 mm, serum level of E 2 was ≥ 100 pg/mL, and serum level of progesterone < 1 ng/mL, 60 mg/day progesterone was intramuscularly injected daily. One blastocyst was thawed and transferred on the sixth day of progesterone injection. Following FET, oral estradiol valerate (6 mg/d) was given continuously, and progesterone oil was replaced by dydrogesterone (30 mg/d) (Abbott, the Netherlands) and vaginal progesterone gel (90 mg) (Crinone, Merck, Germany) daily. Pregnancy was confirmed with serum level of β-HCG > 5 IU/mL 12 days after the FET, clinical pregnancy was diagnosed with the presence of gestational sac by ultrasound examination, ongoing pregnancy was defined as detection of fetal heartbeat at 12 weeks of gestation, and live birth was defined as a live fetus born after 28 weeks of gestation. Only the first FET cycle was included in this study. The primary outcome of this study was the euploidy rate per blastocyst undergoing PGT-A, which was defined as the ratio of the number of euploid embryos to the number of biopsied embryos. The secondary outcomes were the rates of maturation, normal fertilization, day 3 cleavage embryo, high-quality day 3 cleavage embryo, high-quality blastocyst in PGT-A cycle, and rates of implantation, clinical pregnancy, ongoing pregnancy and live birth, and gestational age at delivery, birth weight and height of infants from the first FET cycle. These definitions and calculations were performed in accordance with the Vienna Consensus and the Istanbul Consensus [ 27 , 28 ]: mature oocyte rate (MII oocytes /retrieved oocytes), normal fertilization rate (2PN zygotes/injected oocytes), cleavage rate (day 3 embryos/2PN), blastocyst rate (day 5 embryos/2PN), high-quality blastocyst rate (high-quality day 5 embryos/2PN), aneuploidy rate (aneuploid embryos/biopsied embryos), mosaicism rate (mosaic embryos/biopsied embryos). The outcomes of FET were calculated as: clinical pregnancy rate (number of intrauterine pregnancy cycles with gestational sac at around gestational 6 weeks/number of FET cycles), ongoing pregnancy rate (number of intrauterine pregnancy cycles with live fetus beyond 12 weeks/number of FET cycles), early miscarriage rate (number of natural abortion cycles before 12 weeks/number of clinical pregnancy cycles) and live birth rate (number of delivery with live newborn(s) at least over gestational 28 weeks/number of clinical pregnancy cycles). Statistical analysis was carried out by using the SPSS v 26.0 software (IBM, Armonk, NY, USA). Continuous variables were expressed as means with standard deviations or median (interquartile range) and compared by Student’s t-test or Mann Whitney’s U-test for normal distribution or non-normal distribution data, respectively. Categorical variables were presented as frequency and compared by Chi-square or a Fisher’s exact tests. Fisher’s exact test was used when more than 20% of the cells had an expected frequency less than 5, otherwise, Chi-square was used. Two-tailed P  < 0.05 was indicated as statistical significance. The sample size calculation was based on the assumption that inactivated SARS-CoV-2 vaccination would result in a 15% absolute change in live birth rate. According to data from our center, the live birth rate among PGT patients is approximately 50%. With a two-sided significance level of α = 0.05 and a β error of 0.2 (power = 80%), 173 patients are required per group.

Our results suggested that inoculation with the inactivated SARS-CoV-2 vaccine prior to ovarian stimulation did not adversely affect the euploidy status of blastocysts and subsequent pregnancy outcomes in patients undergoing PGT-A. These results are reassuring for patients and healthcare providers, suggesting that SARS-CoV-2 vaccine can be safely inoculated for patients preparing for assisted reproductive technology treatments without compromising the success rate of these procedures. Nevertheless, it is important to note that our study has limitations such as the relatively short follow-up period and the specific study population. Future studies with larger sample sizes and longer-term follow-up are warranted to confirm these findings and further explore the impact of the inactivated SARS-CoV-2 vaccination on the assisted reproductive technologies.

In this study, we have found that patients inoculated with the SARS-CoV-2 vaccine undergoing PGT-A had similar euploidy rate and outcomes of FET compared with those unvaccinated. Therefore, we propose that the inactivated SARS-CoV-2 vaccine may not affect the ploidy status of embryos, and their development potential and safety of infants. The ploidy is a key factor affecting embryo implantation and pregnancy, and chromosomal abnormalities are one of the important reasons for implantation failure and spontaneous abortion [ 29 ]. Researchers have reported that aneuploid embryos are due to meiotic errors during the formation of gametes, while mosaic embryos are due to mitotic errors during embryo formation after fertilization [ 30 , 31 ]. Premature separation of sister centromeres has been reported as the primary mechanism for aneuploidies [ 32 ], which can increase markedly with ageing, particularly in women over 35 years old [ 33 ]. Other factors may also affect the separation of chromosomes, including the dose of gonadotropin, culture conditions of oocytes and embryos (culture media, pH, temperature, osmolality and oxygen concentration), and laboratory techniques (use of laser and biopsy of cells) [ 34 – 36 ]. However, research on the impact of inactivated SARS-CoV-2 vaccines on embryonic ploidy is scarce. The effect of the vaccination on embryonic euploidy may be related to the autoimmune response to the SARS-CoV-2 vaccine. Reports have suggested that adenovirus vector SARS-CoV-2 vaccines may produce antiphospholipid antibodies (aPL), which could potentially lead to thrombosis and thrombocytopenia in some cases [ 37 ]. Kwak-Kim et al. [ 38 ] have reported that in patients with autoimmune diseases, aPL may accumulate in follicular fluid and bind to the surface of oocytes, thereby affecting oocyte development. Wu et al. [ 39 ] reported a decrease in the number of high-quality embryos and transferable embryos, MII oocytes, blastocysts, high-quality embryos, implantation rate, clinical pregnancy rate, and take-home baby rate in infertile women with aPL. However, to our knowledge, only one study has previously explored the impact of mRNA SARS-CoV-2 vaccines (Pfizer or Moderna) on embryonic ploidy, and found the euploidy rate and aneuploidy rate were no significant difference between vaccinated ( n = 222) and unvaccinated ( n = 983) patients [ 12 ]. Another study also reported the euploidy rate and aneuploidy rate were no significant difference between patients vaccinated with inactivated SARS-CoV-2 vaccines ( n = 66) or not ( n = 67) [ 23 ], which was similar with our study. Therefore, we suggested that inactivated SARS-CoV-2 vaccine may not affect the euploidy status of the embryos. Studies have reported that the LBR, ongoing pregnancy rate, and clinical pregnancy rate in women inoculated with inactivated SARS-CoV-2 vaccines are comparable to those without the vaccination [ 40 , 41 ]. Besides, our study further found that the birth weight and length of newborns were not affected by the inactivated SARS-CoV-2 vaccine, supporting the safety of inactivated SARS-CoV-2 vaccines for endometrial receptivity, pregnancy and infants. Therefore, patients were suggested to be inoculated with the inactivated SARS-CoV-2 vaccine before PGT-A during the COVID-19 pandemic. Our results should be interpreted with caution due to the following restrictions in this study. Firstly, the sample size was relatively small, particularly for the FET cycles. Secondly, all patients have come from a single center. Thirdly, subgroup analysis based on interval of vaccination were not conducted due to small sample size. Fourth, for unvaccinated patients, if they were pregnant after FET, SARS-CoV-2 vaccination was not allowed until they achieved a live birth. While for others, we did not track whether they remained unvaccinated throughout follow-up. Therefore, the results should be interpreted with caution. Further studies with larger sample size, from multiple centers, and with longer follow-ups are thereby required to validate the conclusion.

During the global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 1 ], there have been 772 million confirmed cases, including 6.9 million deaths, as reported by the World Health Organization (WHO). The rapid spread infection and its unprecedented impact on health has promoted vaccination programs to reduce the incidence and mortality. A total of 13.5 billion vaccine doses have been administered, including 3.5 billion doses in China ( https://covid19.who.int/ ). SARS-CoV-2 vaccines are classified by the WHO into inactivated, live attenuated, vector, RNA, DNA, protein subunit, and virus-like particle (VLP) vaccines [ 2 ]. In China, the inactivated SARS-CoV-2 vaccine with lost ability of infection and replication and retained the immune ability has been most widely used [ 3 ]. Inactivated SARS-CoV-2 vaccine was reported to be safe for people aged over 18 years [ 4 ]. However, some studies have doubted the safety of SARS-CoV-2 vaccines in women planning to conceive, therefore their plan for pregnancy was delayed [ 5 , 6 ]. One issue related with the safety of the SARS-CoV-2 vaccine was the interaction between the spike protein of SARS-CoV-2 virus and the human angiotensin-converting enzyme 2 (ACE2) receptors [ 7 ]. ACE2 receptors are abundant in ovarian and testicular tissues [ 8 , 9 ], which has raised concern over detrimental effects on human reproductive system following vaccination. Another reason was the homology between the spike protein of the SARS-CoV-2 and the placental syncytin-1 protein, which may cause infertility [ 10 ]. Therefore, the safety issues of the SARS-CoV-2 vaccine should be taken into consideration for women planning to conceive. Some studies have assessed the impact of the SARS-CoV-2 vaccines on assisted reproductive technology. As reported in countries which mainly used SARS-CoV-2 mRNA vaccine, this kind of vaccine did not affect ovarian reserve, ovarian response to stimulation and outcome of early pregnancy for in vitro fertilization and embryo transfer (IVF-ET) [ 11 – 14 ]. Neither SARS-CoV-2 infection or the mRNA vaccine nor the immune response to them has resulted in measurable detrimental effect on the function of ovarian follicle, including measured Heparan Sulfate Proteoglycans (the major estrogen binding protein) in the follicular fluid [ 15 – 17 ]. The serum level of anti-müllerian hormone (AMH), endometrial receptivity and embryo implantation were also not affected by the vaccine [ 14 , 18 ]. Miller et al. [ 19 ]. have reported that, in a small number of individuals ( n = 48), the live birth rate (LBR), gestational week and birth rate were not significantly different between those with or without vaccination. Studies on the SARS-CoV-2 mRNA vaccines have already traced the outcomes on live birth, whereas research on the inactivated SARS-CoV-2 vaccines in this regard has remains scarce. From April 2021 to January 2023, the SARS-CoV-2 vaccine was inoculated massively in China, with the inactivated SARS-CoV-2 vaccine being the major type ( https://weekly.chinacdc.cn/ ). Some studies have reported that the ovarian response, quality of embryo, and pregnancy outcomes of the IVF-ET cycles were not affected by the inactivated SARS-CoV-2 vaccine in IVF-ET [ 3 , 20 – 22 ]. Euploidy is a marker for good embryonic quality and better chance for live birth, and only one study has reported that embryo ploidy status was similar between patients vaccinated with inactivated SARS-CoV-2 vaccine or not, but without the information of live birth [ 23 ]. By now, most pregnant women inoculated with the inactivated SARS-CoV-2 vaccine before PGT-A have delivered. Therefore, we have compared the euploidy status and LBR in patients inoculated with the inactivated SARS-CoV-2 vaccine and without before PGT-A.