Impact of SARS-CoV-2 Infection on the Course of Pregnancy and Birth After Assisted Reproduction

Abstract

Introduction

The aim of this single center cohort study was to examine the possible effects of SARS-CoV-2 infection, especially the Omicron variant, on outcome of pregnancy and birth after infertility treatment with assisted reproduction.

Material and Methods

A total of 51 pregnancies and births after assisted reproduction were investigated in the period from 01/2022 to 12/2022 in a university fertility center with regards to SARS-CoV-2 infections and vaccination status. Eight multiple pregnancies were assessed separately. 20 women with singleton pregnancy had a confirmed SARS-CoV-2 infection in the six months prior to or during the pregnancy. This group was compared to 23 singleton pregnancies without SARS-CoV-2 infection or with infection had occurred more than six months before assisted reproduction.

Results

The comparison of single pregnancy with or without SARS-CoV-2 showed no differences considering age or body mass index. Complications of pregnancy such as preeclampsia, pregnancy-induced hypertension, placenta previa, placental insufficiency, and preterm labor were also comparable for both groups. There were no significant differences between the two groups with regards to gestational age at delivery, birth weight, birth mode, and APGAR scores. A comparison of the course of pregnancy in women with and women without basic immunization also showed no significant differences.

Conclusion

In the study period of 2022, infection with SARS-CoV-2, in most cases with the Omicron variant, during or up to six months prior to a pregnancy following assisted reproduction did not significantly affect the risk of maternal and fetal complications of pregnancy from the 2nd trimester of pregnancy or the fetoneonatal outcome.

Keywords

preterm birth - viral infection - coronavirus

Introduction

In the years 2020–2022, the COVID-19 pandemic had a severe impact on public life and health care worldwide. In the German federal state of Saxony, almost 2 million cases were reported until May 2023 out of a population of 4 million inhabitants (http://www.coronavirus.sachsen). According to the Robert Koch Institute (RKI), 65.1% of the total population of Saxony was vaccinated (basic immunization) by this point, starting in December 2020 [1]. Compared to other federal states, the immunization rate in Saxony was the lowest rate in Germany. The greatest impact on public life and the highest virus-related death rates were reported in the winter of 2020/2021 before the vaccination roll-out ([Fig. 1]). Nevertheless, the largest number of confirmed infections in Germany was registered in 2022 ([Fig. 1]). The official data show that in 2022, infection was mainly caused by the Omicron variant and, to a lesser extent at the start of the year, by the Delta variant [2].

Fig. 1 7-day incidence (laboratory-confirmed COVID-19 cases per 100000 inhabitants) and weekly deaths in Germany between 2020 and 2023 (according to https://infektionsradar.gesund.bund.de/de/covid, last accessed 10.09.2024).

During the pandemic, fertility treatment using assisted reproduction techniques (ART) such as in-vitro fertilization (IVF) and intracytoplasmic sperm injection continued to be carried out in our university fertility center in Saxony, with the exception of six weeks in the spring of 2020 when all treatments were halted. The number of fertility treatments carried out during the pandemic were similar to those in previous years.

There are only a few studies on the effect of SARS-CoV-2 on ART treatment, the course of pregnancy, and the birth. A comprehensive meta-analysis by Kaur et al. in 2023 [3] included 12 studies on this topic. Three of the studies analyzed the course of pregnancy after the end of the first trimester of pregnancy in 510 women and found no significant difference in the percentage of sustained pregnancies compared to non-infected women. A European study which was already published in 2021 investigated 80 pregnancies after ART and also found that SARS-CoV-2 infection had no significant impact on the course of pregnancy or the birth [4].

Up until the winter of 2021/2022 no couples treated at the university fertility center in Saxony had a SARS-CoV-2 infection before or during ART treatment. In the spring of 2022, an unexpectedly high percentage of miscarriages after ART were noted in addition to increased reports of infections before and, in rare cases, during treatment at the university fertility center. To find out whether infection with SARS-CoV-2 during ART might have led to a higher rate of miscarriages, a prospective observational study and questionnaire-based survey was carried out which looked at infection rates and vaccination status as well as the course of ART treatment and the pregnancy.

A detailed analysis of early pregnancy until the first trimester of 335 ART cycles has already been published by Eckstein et al. in 2023 [5]. Significantly more miscarriages occurred during the study period compared to previous years (p = 0.014). The infections of at least one partner less than six months prior to ART had a significant negative effect on the pregnancy rate (p = 0.010). Infections in women were associated with a significantly higher risk of miscarriage (p = 0.009). However, vaccination against SARS-CoV-2 had a positive effect on the outcome of ART treatment. Treatment cycles in which both or at least one partner had a basic immunization against SARS-CoV-2 were found to lead to a statistically significant higher rate of pregnancies than cycles in unvaccinated couples (p = 0.011).

Following that study, the current study aimed to investigate to what extent SARS-CoV-2 infections up to six months prior to assisted reproduction or during pregnancy and the vaccination status of the woman affected the incidence of complications of pregnancy from the second trimester of pregnancy onward and the birth. Multiple pregnancies were investigated separately from singleton pregnancies as multiple pregnancies are associated with a higher risk of maternal and fetal complications after ART. This has been confirmed by comparisons of the course of singleton and multiple pregnancies after ART based on the German IVF registry [6]. It has been hypothesized that changes in the daily life of pregnant women with twin pregnancies may be different from those of women with singleton pregnancy, and may include inactivity at home, fewer social contacts, and an earlier start to the individual prohibition of employment during pregnancy.

Methods

Study design

The prospective cohort study with follow-up presented here observed pregnancies after assisted reproduction between 01/2022 and 12/2022 in a university fertility center in Germany. The study protocol was approved by the local ethics commission (BO-EK-349082022).

A total of 335 treatment cycles with natural cycle embryo transfers or transfer after controlled ovarian stimulation were carried out in 2022. An embryo transfer was carried out in 214 cycles; this resulted in 78 clinical pregnancies (32.77%). 26 of the pregnancies ended with a miscarriage in the first trimester of pregnancy (33.77%); one of the pregnancies was an extrauterine pregnancy. 51 ART pregnancies continued beyond week 12 + 0 of gestation (GW) and were investigated in this study ([Fig. 2]).

Fig. 2 Graph showing criteria for inclusion in the study.

Pregnancy rates

The pregnancy rate in the 2022 study was 32.77% (78/238 women). The miscarriage rate up until week 12 + 0 of gestation was 26 out of 77 intrauterine pregnancies with a confirmed amniotic sac in 33.77%. For 51 pregnancies (15.22% of all ART cycles with embryo transfer), the pregnancy lasted more than 12 + 0 weeks of gestation.

Data collection

Study-relevant data were extracted from the clinical documentation system and the MediTEX program used for ART treatment. Data on SARS-CoV-2 infections, vaccinations and the course of pregnancy were additionally collected by telephone interview. The data for this study was collected at two different timepoints during pregnancy from the 2nd trimester and after the birth using structured questionnaires (see the online supplement). The data collection period extended from June to September 2023. The response rate for the questionnaire administered after the birth was 98.03%; one woman declined the repeat survey. 28 of the 51 patients gave birth in the university hospital. Detailed clinical data on the course of pregnancy and the birth is available for these patients. A standard feedback form and, in some cases, a doctor’s letter was available for the other patients.

Statistical analysis

Statistical evaluation was carried out using IBM SPSS version 25. Categorical data are presented as absolute and relative frequencies. Metric data are presented as mean ± standard deviation as well as minimum and maximum or alternatively as median with the 25th and 75th percentiles. Groups were compared using Pearson’s chi-square test or Fisher’s exact test for categorical variables. Shapiro-Wilk test was used to test for normal distribution of metric data. Non-normally distributed data were analyzed using Mann-Whitney U-test or Kruskal-Wallis test. A p value of < 0.05 was considered statistically significant in all statistical tests.

Results

Characteristics of the patient population

The study sample consisted of 51 women who met the following inclusion criteria:

1. Onset of pregnancy following ART in a natural or stimulated cycle

2. Continuation of pregnancy beyond week 12 + 0 of gestation

The mean age distribution for all the women was 34.32 years ± 3.22 (25.48–39.28). The mean body mass index (BMI) was 24.72 kg/m² ± 6.28 (16.90–41.52).

Pregnancy course

The graph ([Fig. 3]) shows the period for all pregnancies (bars) and the times of infection with SARS-CoV-2 (diamonds). 15 women had a SARS-CoV-2 infection during pregnancy. Ten infections occurred before pregnancy during the period when the Omicron variant was prevalent.

Fig. 3 Bar chart showing SARS-CoV-2 infections which occurred and the temporal relationship to the onset and course of pregnancy (01/2022–09/2023; n = 51); blue bars are live births, the yellow bar stands for the three pregnancies which ended with late miscarriage (n = 2) or stillbirth (n = 1).

The mean age distribution of the women with multiple pregnancy was 33.51 years ± 3.57 (27.11–37.13). Mean BMI was 23.51 kg/m² ± 3.71 (18.81–29.02). One of the eight women with multiple pregnancy had a late miscarriage. This patient had confirmed SARS-CoV-2 infection. The gestational age at delivery was 36.08 ± 2.99 (31.14–38.86) weeks. The most common complications reported for multiple pregnancy were preterm labor and admission to hospital as an inpatient during pregnancy. This occurred in three of the cases with multiple pregnancy with and without infection with SARS-CoV-2. Infection with SARS-CoV-2 was recorded for two women in the six months prior to ART. Seven women were fully vaccinated against SARS-CoV-2.

SARS-CoV-2 infection and the impact on the course of pregnancy and pregnancy outcome of singleton pregnancies

To assess the impact of SARS-CoV-2 infection, the women with singleton pregnancy were divided into two groups ([Table 1]). The mean age distribution of the group of women with singleton pregnancy (n = 43) was 34.47 years ± 3.18 (25.48–39.28). The mean BMI was 24.94 kg/m² ± 6.65 (16.90–41.52).

Table 1 Comparison of characteristics relating to the course of pregnancy and the birth for women with/without SARS-CoV-2 infection. Analysis was done with Fisher’s exact test and Mann-Whitney U-test (significance level p < 0.05). Numbers (percentage) and median (IQB – interquartile range).

Characteristics	Without SARS-CoV-2 infection < 6 months prior to ART	With SARS-CoV-2 infection < 6 months prior to ART and/or during pregnancy	p value (Fisher’s exact test; Mann-Whitney U-test)
Course of pregnancy
Complications of pregnancy	19/23 (82.61%)	18/20 (90.00)	0.669
GDM	9/23 (39.13%)	2/19 (10.53%)	0.075
Bleeding from 2nd trimester	2/23 (8.70%)	2/19 (10.53%)	1.000
Preeclampsia	2/23 (8.70%)	0/19 (0.00%)	0.492
Hypertension during pregnancy	4/23 (17.39%)	2/19 (10.53%)	0.673
Placenta previa	2/23 (8.70%)	3/19 (15.79%)	0.644
Placental insufficiency	3/23 (13.04%)	1/19 (5.26%)	0.613
Preterm labor	2/23 (8.70%)	3/19 (15.79%)	0.644
Admission to hospital as an inpatient during pregnancy	3/23 (13.04%)	2/20 (10.00%)	1.000
Birth
Late miscarriage in GW 12–24	0/23 (0.00%)	1/20 (5.00%)	0.465
Stillbirth	1/23 (4.35%)	0/19 (0.00%)	1.000
Eventful course (late miscarriage/ stillbirth)	1/23 (4.35%)	1/20 (5.00%)	1.000
Preterm birth	2/23 (8.70%)	1/19 (5.26%)	1.000
Gestational age at delivery (weeks)	39.43 (38.00–40.29)	39.86 (38.57–41.00)	0.312
Birth weight (g)	3210 (3005–3633)	3445 (3180–3870)	0.137
Spontaneous birth	16/23 (69.57%)	11/19 (57.89%)	0.432
Good APGAR score, no adaptation disorders	17/22 (77.27%)	17/19 (89.47%)	0.419

Five women had confirmed SARS-CoV-2 infection in the six months prior to pregnancy. Eleven women had SARS-CoV-2 infection during pregnancy. Four women had SARS-CoV-2 infection both before and during pregnancy. The control group without infection consisted of 23 women who either had not had SARS-CoV-2 infection or had confirmed SARS-CoV-2 infection more than six months prior to ART treatment. There were no differences between the two groups with regards to age (without infection: 34.61 years [32.41–36.50] vs. with infection 35.26 years [33.97–36.77]; p = 0.436) or body mass index (without infection 22.76 kg/m² [20–31–29.32] vs. with infection 22.92 kg/m² [21.24–25.37]; p = 0.893). Complications of pregnancy were reported for 82.61% of women without SARS-CoV-2 infection and for 90% of women with confirmed infection (p = 0.669). When they were questioned in the context of the study protocol, the women reported a mean of 1.9 complications of pregnancy. There was no difference between the groups with or without infection (p = 0.669). There was also no overall difference between the two groups with regards to the course of pregnancy as a function of SARS-CoV-2 infection ([Table 1]). Unexpectedly, however, a considerable percentage of the women without infection were diagnosed with gestational diabetes (GDM) (39.13% vs. 10.53%; p = 0.075). There were no significant differences between the groups with regards to other investigated complications such as preeclampsia, pregnancy-induced hypertension, placenta previa, placental insufficiency, and preterm labor. Admission to hospital as an inpatient during pregnancy did not occur more often in the group of women with SARS-CoV-2 infection before or during pregnancy.

Statistical analysis found no significant differences between the two groups for the outcome variables “Gestational age at delivery” (p = 0.312) and “Birth weight” (p = 0.137). This also applied to “Birth mode” (= percentage of spontaneous births) and “APGAR score” of the infant (= percentage with a good APGAR score).

SARS-CoV-2 immunization and impact on complications/outcome

65.12% of the women with singleton pregnancy who participated in the study were classified as having basic immunization. The definition of basic immunization includes at least two vaccinations as well as either confirmed infection with SARS-CoV-2 or a third booster vaccination [7]. When the course of pregnancy was analyzed, serious complications occurred in a small percentage of both groups, i.e., with and without basic immunization. A stillbirth occurred in the group of pregnant women without SARS-CoV-2 immunization during the study period, while one woman with basic immunization had a late miscarriage. With regards to other complications, the analysis showed that the rate of preterm births (13.33% vs. 3.70% – [Table 2]) and the rate of inpatient treatments (20.00% vs. 7.14%) tended to be higher in the group of non-immunized women. Because of the limited sample size the differences were not statistically significant.

Table 2 SARS-CoV-2 vaccination status and impact on the course of pregnancy.

Characteristics	Without immunization	With immunization	p value (Fisher’s exact test)
Late miscarriage in GW 12–24	0/15 (0.00%)	1/28 (3.57%)	1.000
Stillbirth	1/15 (6.70%)	0/27 (0.00%)	0.357
Eventful course of pregnancy (late miscarriage/stillbirth)	1/15 (6.70%)	1/28 (3.57%)	1.000
Preterm birth	2/15 (13.33%)	1/27 (3.70%)	0.287
Admission to hospital as an inpatient during pregnancy	3/15 (20.00%)	2/28 (10.00%)	0.324

Discussion

2022 was the first year in which a large part of the population in Germany had a SARS-CoV-2 infection. This single-center prospective study covers the period of 2022, the peak phase of the pandemic. The living situation of pregnant women in 2022 was affected by the unknown impact of an infection with SARS-CoV-2 on the health of the child. Many pregnant women faced the challenges of having to avoid social contacts, needing to be vaccinated, having to withdraw from professional activities, systematic testing, quarantine in the event of confirmed infection, and worries about complications in pregnancy from infections and vaccinations.

At the start of the pandemic, public forums and studies debated whether SARS-CoV-2 infections would lead to a higher risk of miscarriage. An international systematic review published in 2021 [8] highlighted the higher risk emanating from an infection of the trophoblast or the placenta. The suspicion already arose in 2020 that vascular changes [9] caused by coagulation activation and vasculitis in the uteroplacental stromal bed by infection with SARS-CoV-2 could increase the risk of miscarriage. A British study which carried out an online survey [10] found a higher risk of early miscarriage based on the data of 3041 women. The relative risk of miscarriage at a mean of GW 9 was 1.7 after infection compared to non-infected women.

A Spanish study [11] which collected data during the first two waves of the pandemic came to the conclusion that pregnancies with SARS-CoV-2 infection had a higher risk of maternal complications such as diabetes mellitus, gestational diabetes, obesity, and arterial hypertension but that there were no demonstrable effects on the course of pregnancy.

The German CRONOS study [12] which evaluated the impact of infection with the SARS-CoV-2 pathogen during pregnancy on maternal and infant health included a total of 8782 women for the period from March 2020 to December 2022. The data of these women was passed on to the registry by the medical staff. It can be assumed that the active process of reporting information to a registry indicates that the reported events were particularly severe course of disease and late infection. In fact, 40% of infected women were admitted to hospital as inpatients and only 5% of the reported infections occurred in the 1st trimester of pregnancy [12]. Analysis of the registry data shows that the risk of specific COVID-19-related events was low if the women were infected with COVID-19 in the first trimester. The risk increased if infection occurred at a later date in pregnancy up until the early part of the third trimester. In the second period of data collection, which took place in the first half of 2022, i.e., over the same period as that covered by our study, the effects of infection were lower than in 2020/2021. Vaccination against SARS-CoV-2 was associated with lower fetomaternal risks.

A national retrospective cohort study from South Korea which used registry data of pregnant women with and without SARS-CoV-2 infection [13] investigated the impact of infection during pregnancy. The study compared more than 367000 pregnancies without and 2158 pregnancies with infection over a period of 2 years during the period of infection with the Delta to Omicron variants. The reported percentage of 0.58% infections in all analyzed pregnancies is low. Although the number of pregnant women and neonates requiring intensive care significantly increased by a factor of 2–3 over that period, there was no pronounced increased risk of maternofetal complications. The only statistically significant increase was the risk of intrapartum or postpartum bleeding during the phase of infection with the Delta variant. The study showed that, overall, the possible impact on pregnancy was lowest at the time of the Omicron variant. The positive effect of vaccination on the course of infection during pregnancy was discussed.

Our study from Saxony which reviewed pregnancies in 2022 found higher rates of infection compared to previous studies; however, the study also included infections which occurred before the start of pregnancy (a total of 46.51% of women). Because of ART treatment and the prospective study design which already began to collect data before the start of pregnancy, the statements on infections before the start of pregnancy and in the first weeks of pregnancy are especially reliable. In contrast to the studies discussed above, most infections in our study were caused by the Omicron variant. Compared to earlier variants such as Alpha or Delta, Omicron is characterized by higher virulence but lower pathogenicity [14].

Although serious complications such as late miscarriage and stillbirth occurred in 2 of 51 pregnancies which continued beyond week 12+0 of gestation, no significant association between complications and infections or vaccination status was identified. Most of the women included in the study were young and healthy women of reproductive age who mainly experienced a mild to moderate course of infection with SARS-CoV-2. It is assumed that in 2022, women with serious prior disease continued to postpone ART treatment during the time of the pandemic.

Our study included singleton pregnancies after ART to estimate the impact of infections. A comprehensive meta-analysis by Kaur et al. from 2023 [3] investigated the relationship between SARS-CoV-2 infections prior to ART treatment and possible effects on the course of assisted reproduction. Three studies (Youngster et al., Barkat et al. und Aizer et al.) [15] [16] [17] reported no significant differences in the sustained rate of pregnancy between infected and non-infected women. However, their analysis also included pregnancies after ART treatment in women with infections who abstained from fresh embryo transfer and opted for a freeze-all approach and a time-delayed transfer. This means that the transient effect of an infection on the course of pregnancy due to factors such as changes to the endometrium, placentation and thrombogenicity are not taken into account.

An EU study carried out in 2021 by Ata et al. [4] investigated the possible impact of infection during ART (n = 11) or pregnancy in the early stage of the pandemic on the course of pregnancy, the complication rate, and the live birth rate. The study analyzed 80 reported pregnancies after assisted reproduction and confirmed infection. This first observational study without a control group on the possible effects of infection found that 10 of the pregnancies ended with miscarriage (12.5%) and 2 with a stillbirth (2.5%). More than 60% of women were delivered by caesarean section. After taking reporting bias into account, i.e., the probability that only more severe cases were reported, the conclusion on publication of the study in 2021 was viewed as providing reassurance about the uncomplicated course of pregnancy despite infection during of ART or pregnancy.

Our own study of 51 pregnancies reported a few serious complications. Two women with SARS-CoV-2 infection had late miscarriages; one women without infection who had not been vaccinated had a stillbirth. There is no presumption about any association with infection or vaccination. There may be many reasons for an eventful course of pregnancy, e.g., identifiable predisposing factors for stillbirth such as placental dysfunction disorders with placental insufficiency affecting the fetus.

The percentage of women delivered by caesarean section did not differ significantly between the group with and the group without SARS-CoV-2 infection (30% of women without infection vs. about 40% of women with infection). During the first stages of the pandemic, elective caesarean sections were carried out more often worldwide in pregnant women with SARS-CoV-2 infection, especially towards the end of pregnancy [18]. The reasons for this were, on the one hand, an attempt to lower the risk of infection for the hospital staff, and, on the other hand, worries about a possible negative impact on the health of mother and infant caused by the still unknown infection. Recommendations were amended over the course of 2022, and thereafter the indications for delivery by caesarean section were based more on medical criteria again and less on infection with SARS-CoV-2 [18]. Following this change, the percentage of spontaneous deliveries of infected pregnant women was closer to the percentages reported for standard obstetric procedures.

An Italian study from the first year of the pandemic showed that the clinical pregnancy and miscarriage rates of couples without confirmed infection at the time of ART treatment were comparable to those before the time of the pandemic [19]. The live birth rate also remained unchanged. A retrospective Indian study by Banker et al. in 2022 [20] investigated 367 IVF cycles from the first months of the pandemic. Infection with SARS-CoV-2 was only confirmed in 6.8% of women with embryo transfer after stimulation and 3.9% of women with cryotransfers as well as 10% of pregnant women. No significant differences were found in clinical and biological reproduction outcome parameters after ART treatment during the pandemic compared to the time before the start of the pandemic. The most common prenatal complications were gestational diabetes and pregnancy-related hypertension.

A subanalysis of the CRONOS study data by Ziert et al. published in 2022 [21] compared 65 pregnancies after ART with 1420 spontaneous pregnancies. Severe SARS-CoV-2 did not occur more often in women with ART pregnancy than in the comparison group. A higher risk of complications of pregnancy after ART could be ascribed to factors such as older age, multiple pregnancy, and obesity. The risk of miscarriage could not be analyzed because the case numbers for documented pregnancies were too low.

Overall, the results of the studies indicate that infection with SARS-CoV-2 prior to and during pregnancy does not significantly affect the course of pregnancy after ART. Our study confirms this assessment also for the stage of the pandemic in 2022 when most infections were classified as being caused by the Omicron variant.

Vaccination against SARS-CoV-2 also showed no higher risk of an unfavorable course of fertility treatment or pregnancy, as demonstrated by a meta-analysis [22] which included 21 studies and a further meta-analysis [23] of 20 studies covering a total of 18877 ART treatment cycles compared to non-vaccinated women. A population-based study from the United Kingdom [24] found no connection between vaccination and miscarriage compared to non-vaccinated women before the pandemic. The Intercovid 2022 study [25] even showed that neonates born to vaccinated mothers had a lower risk of preterm birth or unfavorable neonatal development. In fact, the neonates born to mothers who had a booster vaccination showed the highest vaccine effectiveness. Our study showed that women who had basic immunization had a distinctly lower risk of preterm birth (3.70%) compared to women had not been vaccinated (13.33%). But because the numbers were low, this difference was not significant.

A recent meta-analysis of the Omicron wave [26] which included 862272 women, 308428 of whom were vaccinated, showed that the risk of stillbirth decreased by 45% following vaccination during pregnancy. The risk of preterm birth before week 32 + 0 of gestation decreased by 33% and the risk of requiring admission to hospital as an inpatient was also significantly lower (20%) after being vaccinated in pregnancy. The pregnant woman who had a stillbirth in our study did not have confirmed infection but she also did not have basic immunization against SARS-CoV-2.

There were no admissions to hospital for SARS-CoV-2 infection in the study period, but the tendency was that the percentage of women generally admitted to hospital during pregnancy was lower for vaccinated women (7.14% vs. 20.00%).

A Spanish study [27] of 510 vaccinated women found that vaccination did not have a negative impact on the course of ART treatment and ovarian reserve. The analysis of our data even showed a statistically significant higher pregnancy rate for treatment cycles in women whose partner had basic immune protection against SARS-CoV-2 compared to cycles in women whose partner had not been immunized [5]. This effect can probably be ascribed to the reduced risk of infection.

Vaccination appears to significantly decrease the risk of complications in early pregnancy. Our results and the latest studies clearly show that immunization does not have a negative impact on either the course of fertility treatment or the further course of pregnancy after the 2nd trimester. These findings emphasize the role of vaccination against SARS-CoV-2 as a preventive measure to improve maternal and fetal health during the pandemic.

Strengths and Limitations

Our prospective single-center cohort study on SARS-CoV-2 infection and vaccination in couples undergoing ART treatment in 2022 is a study with framework conditions that will never occur in this form again in future. The Coronavirus Test Ordinance ensured that testing coverage against SARS-CoV-2 infection was almost 100% for the entire sample, which markedly increased the data quality on infection. The strengths of this study are the high participation rate, which was almost 100%, and the fact that respondents were questioned about the infection and vaccination status of both partners at two different timepoints, i.e., during pregnancy and after the birth. Complications of pregnancy were comprehensively covered in the questionnaire and could be additionally confirmed for a majority of the patients using information recorded about the birth which was available for the patients who gave birth at the center (51%). This reinforces the validity of our findings.

The limitations of the study are its small sample size of 43 women with singleton pregnancy after ART in a fertility center in Saxony during a specific period of the pandemic. This limits the generalizability of the results. The information about infections was based on self-disclosure by study participants after testing in accordance with the Coronavirus Test Ordinance. It was not possible to obtain a reliable antibody status about SARS-CoV-2 infections as there were no established clinical markers for SARS-CoV-2 immunity at the time of the study. It is possible that asymptomatic infections were not sufficiently reported and that the percentage of undetected infections could be several times higher than the number of confirmed cases, which would affect the quality of the data [28].

Conclusion

The results of this study showed no significant differences between the groups with regards to complications, the course of pregnancy, and pregnancy outcome in women with a SARS-CoV-2 infection before or during pregnancy following ART treatment and women without SARS-CoV-2 infection. A comparison of the groups also found no significant differences between women who had been immunized and those who had not been immunized against SARS-CoV-2. Because of the many different effects of SARS-CoV-2 infections and possible health impacts, these study results cannot be generalized and cannot be transferred to other waves of infection.

Supplementary Material

Questionnaire: Impact of SARS-Covid-19 Infection on the Course of Pregnancy and Birth.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

Our grateful thanks go to everyone who participated in this survey, without whom this work would not have been possible.

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Publication History

Received: 27 September 2024

Accepted after revision: 07 December 2024

Article published online:
19 May 2025