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Review
. 2023 May;119(5):772-783.
doi: 10.1016/j.fertnstert.2023.01.024. Epub 2023 Jan 23.

Effect of female coronavirus disease 2019 vaccination on assisted reproductive outcomes: a systematic review and meta-analysis

Jialyu Huang  1 , Zheng Fang  2 , Yiqi Liu  3 , Chutian Xing  3 , Lingling Huang  1 , Jiaqin Mao  2 , Houyang Chen  1 , Zhihui Huang  1 , Leizhen Xia  1 , Liang Tang  1 , Zhiqin Zhang  1 , Bingqin Liu  4 , Hua Huang  1 , Lifeng Tian  1 , Xiaoyan Ai  5 , Qiongfang Wu  6
Affiliations
Review

Effect of female coronavirus disease 2019 vaccination on assisted reproductive outcomes: a systematic review and meta-analysis

Jialyu Huang et al. Fertil Steril. 2023 May.

Abstract
in English, Spanish

Importance: The effect of coronavirus disease 2019 (COVID-19) vaccination on fertility warrants clarification in women undergoing assisted reproductive treatment.

Objective: To study the association between female COVID-19 vaccination and outcomes of assisted reproductive treatment.

Data sources: PubMed, Embase, the Web of Science, Cochrane Library, and medRxiv and bioRxiv were searched for eligible studies from December 1, 2019, to November 30, 2022, with no language restrictions.

Study selection and synthesis: Observational studies comparing assisted reproductive outcomes between women with and without COVID-19 vaccination were included. The pooled estimates were calculated using the random-effects models as mean differences (MDs), standardized MDs, or odds ratios with 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic.

Main outcomes: The number of oocytes retrieved and clinical pregnancy rate.

Results: Twenty-one cohort studies involving a total of 19,687 treatment cycles were included. In a comparison of the vaccinated vs. unvaccinated groups, the pooled MD for oocyte number was -0.06 (95% CI, -0.51 to 0.39; I2 = 0), and the pooled odds ratio for clinical pregnancy was 0.95 (95% CI, 0.85-1.05; I2 = 0). Similarly, there were no statistically significant adverse effects identified in other outcomes determined a priori, including 4 cycle characteristics, 6 laboratory parameters, and 3 pregnancy indicators. Most results were consistently unchanged in subgroup and sensitivity analyses, with no evidence of publication bias according to Egger's test.

Conclusion and relevance: Our work did not find significant differences in assisted reproductive outcomes between vaccinated and unvaccinated women. However, more data are warranted to confirm the safety of COVID-19 vaccination for assisted reproductive treatment and in female fertility in general.

Efectos de la vacunación femenina para la enfermedad del coronavirus 2019 en los resultados de reproducción asistida: revisión sistemática y meta-análisis.

Importancia: el efecto de la vacunación para la enfermedad del coronavirus 2019 (COVID-19) en la fertilidad merece una aclaración en mujeres que se someten a un tratamiento de reproducción asistida.

Objetivo: Estudiar la asociación entre la vacunación contra el COVID-19 y los resultados de los tratamientos de reproducción asistida.

Fuentes de la data: Se buscaron estudios elegibles en PubMed, Embase, la web de la ciencia, Librería Cochrane, y medRxiv y bioRxiv desde Diciembre 1, 2019 a Noviembre 30, 2022, sin restricciones en el idioma.

Selección del estudio y síntesis: Se incluyeron estudios observacionales comparando los resultados de reproducción asistida entre mujeres con o sin vacunación contra COVID-19. La estimación agrupada fue calculada usando los modelos aleatorios-efectos como diferencias media (MDs), MDs estandarizada, o con razón de momios con 95% de intervalo de confianza (CIs). La heterogeneidad fue valorada usando estadista l2.

Resultados principales: número de óvulos recuperados y tasa de embarazo clínico.

Resultados: Se incluyeron veinte y un estudios de cohorte incluyendo un total de 19.687 ciclos de tratamiento. En una comparación de los grupos vacunados vs no vacunados, la MD agrupadas para óvulos maduros fue 0.06 (95% CI_0.51 a 0.39;I2 ¼ 0), y la razón de momios agrupadas para embarazo clínico fue 0.95 (95% CI, 0.85-1.05; I2 ¼ 0). De forma similar no hubo diferencias estadísticamente significativas en la identificación de efectos adversos en otros resultados determinados a priori, incluyendo 4 características de ciclos, 6 parámetros de laboratorio y 3 indicadores de embarazo. Muchos resultados fueron consistentemente sin cambios en los análisis sensitivos y subgrupales, sin evidencia de bias en la publicación acorde al test de Egger’s.

Conclusiones y relevancia: Nuestro trabajo no encontró diferencias significativas entre los resultados de reproducción asistida de mujeres vacunadas y no vacunadas. Sin embrago, se necesitan más datos para confirmar la seguridad de la vacunación contra COVID -19 para los tratamientos de reproducción asistida y para las fertilidad femenina en general.

Keywords: COVID-19; SARS-CoV-2; assisted reproductive technology; fertility; vaccine.

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Figures

Figure 1
Figure 1
The flow diagram of study selection. IVF = in vitro fertilization.
Figure 2
Figure 2
Forest plot of (A) oocyte number and (B) clinical pregnancy for vaccinated vs. unvaccinated cycles according to different vaccine types. CI = confidence interval; mRNA = messenger ribonucleic acid.
Supplementary Figure S1
Supplementary Figure S1
Forest plot of cycle characteristics for vaccinated versus unvaccinated cycles. (A) Stimulation duration. (B) Gonadotropin dose. (C) Peak estradiol level. (D) Endometrial thickness.
Supplementary Figure S2
Supplementary Figure S2
Forest plot of laboratory parameters for vaccinated versus unvaccinated cycles. (A) Number of oocytes retrieved. (B) Mature oocyte rate. (C) Fertilization rate. (D) Cleavage rate. (E) Good-quality embryo rate. (F) Blastocyst formation rate. (G) Euploidy rate. ET, embryo transfer.
Supplementary Figure S3
Supplementary Figure S3
Forest plot of fertility outcomes for vaccinated versus unvaccinated cycles. (A) Biochemical pregnancy. (B) Clinical pregnancy. (C) Embryo implantation. (D) Ongoing pregnancy.
Supplementary Figure S4
Supplementary Figure S4
Forest plot of clinical pregnancy for vaccinated versus unvaccinated cycles according to different embryo transfer strategies. FET, frozen-thawed embryo transfer.
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