Published 2024 – 2025 | Version v6
Preprint Open

Optimizing care for women experiencing pregnancy loss: Insights from a systematic review and meta-analysis

Authors/Creators

  • 1. Government Erode Medical College and Hospital
  • 2. Department of Pharmacology
  • 3. ROR icon Mid Yorkshire Hospitals NHS Trust
  • 4. ROR icon Government Vellore Medical College

Contributors

  • 1. Government Erode Medical College and Hospital
  • 2. ROR icon Mid Yorkshire Hospitals NHS Trust
  • 3. Department of Obstetrics and Gynaecology
  • 4. ROR icon Government Vellore Medical College

Description

Title: Optimizing Care for Women Experiencing Pregnancy Loss: Insights from a Systematic Review and Meta-Analysis

This systematic review and meta-analysis was developed to comprehensively assess interventions targeting clinical and psychological outcomes for women experiencing pregnancy loss. The PRISMA checklist ensures the study adheres to rigorous standards for transparency, reproducibility, and methodological integrity. Below is a detailed account of how each checklist item was addressed in this research.

Title and Registration (Items 1–2)

The title of the study explicitly identifies it as a systematic review and meta-analysis, signaling the methodology employed. The study was registered with PROSPERO under the ID CRD42025635112, ensuring public accessibility and accountability. This registration includes a detailed protocol that outlines the study’s objectives, eligibility criteria, and planned analyses, safeguarding transparency.

Authors and Contributions (Items 3a–3b)

The authors of this study are Dr. Prieyadharshini Jayaprakasam (Mid Yorkshire NHS Trust, UK), Dr. Jeyaram Nadarajan Saraswathy (Government Vellore Medical College, India), and Dr. Arbind Kumar Choudhary (Government Erode Medical College, India). Dr. Jayaprakasam conceptualized the study and designed the framework. Dr. Saraswathy was responsible for data collection, screening, and quality assessment of studies, while Dr. Choudhary led the statistical analyses and manuscript preparation. The diverse expertise of the team ensures methodological rigor and practical relevance.

Rationale and Objectives (Items 7–8)

The rationale for this study stems from the significant clinical and psychological burden caused by pregnancy loss, which affects millions of women globally. Interventions such as pharmacological therapies, psychological support, and assisted reproductive technologies (ART) hold promise for improving outcomes but require comprehensive evaluation. The objective was to assess the effectiveness of these interventions using a systematic and evidence-based approach.

Eligibility Criteria and Information Sources (Items 9–10)

Eligibility criteria were clearly defined to include studies published between 2020 and 2024 that evaluated interventions for pregnancy loss. Non-English studies and those with insufficient data were excluded to maintain focus and ensure data reliability. Information sources included PubMed, Cochrane CENTRAL, EMBASE, CINAHL, Scopus, and manual citation searches, ensuring a comprehensive literature review.

Search Strategy and Study Records (Items 11–12)

The search strategy was tailored for each database and included terms such as “pregnancy loss,” “ART interventions,” “mifepristone,” “misoprostol,” and “mindfulness therapy.” The search strategy was detailed in the protocol to enable reproducibility. All study records were systematically managed using Mendeley reference management software, where duplicates were identified and removed.

Selection and Data Collection Processes (Items 13a–13b)

The study selection process involved two independent reviewers screening titles, abstracts, and full texts against predefined criteria. Any discrepancies were resolved by a third reviewer to minimize bias. Data were extracted using a standardized template that included intervention details, outcomes, and population characteristics. This template ensured consistency in data collection and facilitated comprehensive analysis.

Data Items and Outcomes (Items 14–15)

The primary outcomes of interest were clinical pregnancy and live birth rates. Secondary outcomes included psychological measures such as stress reduction, patient satisfaction, and mental health improvements. Data on tissue expulsion rates and adverse effects were also extracted for pharmacological interventions. These outcomes were chosen to address both physical and emotional aspects of pregnancy loss.

Risk of Bias and Data Synthesis (Items 16–17)

The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for observational studies. Meta-analysis was conducted using Review Manager (RevMan), with heterogeneity assessed via the I² statistic. Subgroup analyses explored variations in outcomes based on pregnancy loss types, geographic regions, and healthcare settings. Sensitivity analyses were performed to evaluate the robustness of the results.

Meta-Biases and Confidence in Evidence (Items 18–19)

Publication bias was assessed using funnel plots and Egger’s regression test. No significant publication bias was detected. The GRADE framework was applied to evaluate the quality of evidence for each outcome, providing confidence in the reliability of findings.

Reporting and Dissemination Plans (Items 20–21)

The study was reported in accordance with PRISMA guidelines, with dedicated sections for methods, results, discussion, and conclusions. Findings will be disseminated through peer-reviewed journal publications and presentations at obstetrics and gynecology conferences, ensuring widespread accessibility.

Timelines and Ethics (Items 22–23)

The study was conducted between 2020 and 2024, with publication planned for 2025. Ethical approval was not required, as the study exclusively utilized published data and did not involve human or animal participants.

Amendments and Accessibility (Items 24–25)

Any amendments to the protocol will be recorded in PROSPERO and detailed in future publications. The protocol and extended data, including the PRISMA-P checklist, analyzed figures, and data templates, are publicly accessible on Zenodo (DOI: 10.5281/zenodo.14679477).

Review Team and Funding (Items 26–27)

The review team comprises experts in obstetrics (Dr. Jayaprakasam), gynecology (Dr. Saraswathy), and pharmacology (Dr. Choudhary). No external funding or sponsorship was received; the study was independently conducted by the authors.

Abstract (English)

Optimizing Care for Women Experiencing Pregnancy Loss: Insights from a Systematic Review and Meta-Analysis

Prieyadharshini Jayaprakasam, Jeyaram Nadarajan Saraswathy, Arbind Kumar Choudhary

Affiliation:

1. Dr. Prieyadharshini Jayaprakasam

Department of Obstetrics and Gynaecology

Mid Yorkshire NHS Trust, Wakefield

Postcode: WF1 4DG, United Kingdom

Email: p.jayaprakasam@nhs.net

2. Dr. Jeyaram Nadarajan Saraswathy

Department of Obstetrics and Gynaecology

Government Vellore Medical College, Vellore

Postcode: 632011, India

Email: jairam.cr@gmail.com

3. Dr. Arbind Kumar Chaudhary, Assistant Professor of Pharmacology, Government Erode Medical College and Hospital, Tamil Nadu, India(ORCIDID: https://orcid.org/0000-0001-8910-1745; Email: arbindkch@gmail.com; Phone: +91 78717 97278).

Corresponding Author:

Dr. Arbind Kumar Chaudhary, Assistant Professor of Pharmacology, Government Erode Medical College and Hospital, Tamil Nadu, India(ORCIDID: https://orcid.org/0000-0001-8910-1745; Email: arbindkch@gmail.com; Phone: +91 78717 97278).

Abstract

Background

Pregnancy loss, including miscarriage, stillbirth, and early losses, affects millions globally. Approximately 15-20% of pregnancies end in miscarriage, with recurrent pregnancy loss (RPL) affecting 1-2% of couples. This systematic review and meta-analysis evaluated the effectiveness of pharmacological, psychological, and assisted reproductive technology (ART) interventions in improving clinical and psychological outcomes for women experiencing pregnancy loss.

Objective

To assess the impact of pharmacological, psychological, and ART interventions on clinical and psychological outcomes in women experiencing pregnancy loss and identify gaps in healthcare delivery.

Methods

Following PRISMA guidelines, 30 studies published between 2020 and 2024 were analyzed using data from PubMed, Cochrane Library, and Embase. Studies were included if they assessed interventions for pregnancy loss, focusing on pharmacological therapies, psychological approaches, and ART. Statistical heterogeneity (I² statistic) and publication bias (Egger’s regression test) were evaluated. Subgroup and sensitivity analyses explored variations across geographic, demographic, and methodological factors.

Results

Pharmacological therapies, including mifepristone and misoprostol, significantly improved tissue expulsion (OR = 3.5, 95% CI: 2.8–4.3) and patient satisfaction. Low-dose aspirin increased live birth rates by 22% (RR = 1.22, 95% CI: 1.10–1.35). Psychological interventions such as mindfulness and art therapy reduced stress (SMD = -0.48, 95% CI: -0.65 to -0.30) and enhanced quality of life. ART interventions, especially immediate frozen embryo transfer (FET), improved clinical pregnancy rates (RR = 1.15, 95% CI: 1.07–1.23). Subgroup analyses identified lower intervention efficacy in low-resource settings, while home-based misoprostol showed safety but limited efficacy in reducing postpartum hemorrhage.

Conclusion

Integrated care approaches addressing both physical and psychological needs are effective for managing pregnancy loss. Future research should focus on optimizing protocols, addressing disparities, and ensuring equitable access to care, offering a robust evidence base for improving outcomes.

Keywords: pregnancy loss; recurrent pregnancy loss; pharmacological interventions; psychological interventions; assisted reproductive technologies; frozen embryo transfer; healthcare disparities; meta-analysis.

Methods (English)

Methods

Study Design

This study employed a systematic review and meta-analysis to evaluate the impact of various interventions on psychological and clinical outcomes in women experiencing pregnancy-related challenges. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to ensure transparency and rigor in the review process. Additionally, the PICO framework (Population, Intervention, Comparator, Outcomes) was used to structure the research question and guide data synthesis.

 

PRISMA Flow Diagram

The PRISMA flowchart mapped the study selection process as follows:

• A total of 1,200 records were identified through database searches (PubMed: 600, Embase: 400, Cochrane: 200) and an additional 40 records were retrieved manually.

• After removing 190 duplicates, 1,050 records were screened based on title and abstract.

• Of these, 100 full-text articles were assessed for eligibility, and 82 were excluded for the following reasons:

o 50 articles: Irrelevant population.

o 20 articles: Unsuitable study design.

o 12 articles: Insufficient data.

• A total of 18 studies met the inclusion criteria and were included in the qualitative and quantitative synthesis.

 

PICO Framework

The PICO framework structured the study as follows:

• Population: Women experiencing early pregnancy loss, recurrent pregnancy loss, undergoing assisted reproductive technologies (ART), or receiving antenatal care.

• Intervention: Various approaches, including mifepristone + misoprostol, mindfulness therapy, art therapy, low-dose aspirin, early essential newborn care (EENC), and frozen embryo transfer (FET) strategies.

• Comparator: Placebo, misoprostol alone, routine antenatal care, delayed transfer, or no intervention.

• Outcomes:

o Primary Outcomes: Tissue expulsion success, pregnancy rates, live birth rates, and mental health improvement.

o Secondary Outcomes: Reduction in biochemical loss, maternal satisfaction, depression scores, and adverse effects.

Data Sources and Search Strategy

Comprehensive searches were conducted in PubMed, Embase, and the Cochrane Library using a combination of medical subject headings (MeSH) terms and keywords. Additional studies were identified through manual searches of references in related articles.

 

Eligibility Criteria

• Inclusion Criteria:

Studies involving relevant populations and interventions as defined in the PICO framework were included. Both randomized controlled trials (RCTs) and observational studies reporting primary and secondary outcomes were considered.

• Exclusion Criteria:

Studies with insufficient data, non-human research, or irrelevant populations were excluded. Duplicate studies and those deemed to have high risk of bias were also removed.

Data Extraction

A standardized data extraction form was used to collect study characteristics (e.g., study design, year, location, population size), intervention details (e.g., duration, mode of delivery, components), and outcomes (primary and secondary). Two reviewers independently extracted the data to ensure accuracy and consistency.

 

Quality Assessment

The quality of included studies was assessed using validated tools:

• The Cochrane Risk of Bias Tool was applied to RCTs.

• The Newcastle-Ottawa Scale (NOS) was used for cohort and observational studies.

Discrepancies between reviewers were resolved through discussion or consultation with a third reviewer.

 

Statistical Analysis

Quantitative data were synthesized using a random-effects meta-analysis to pool effect sizes. Heterogeneity was assessed using Cochran’s Q statistic and I2I^2I2 values. Publication bias was evaluated with funnel plots and Egger’s regression test for asymmetry. Meta-regression analyses examined the impact of moderator variables (e.g., intervention duration, delivery method, population characteristics) on psychological outcomes. Subgroup analyses explored variations by type of pregnancy loss, intervention type, and geographic setting (developed vs. developing countries).

 

Thematic Synthesis

Qualitative data were synthesized using thematic analysis to explore patient and provider experiences, as well as barriers and facilitators. Data were coded and categorized into key themes.

 

Software and Tools

Data analyses were performed using RevMan (Review Manager (RevMan) [Computer program]. Version 5.4, The Cochrane Collaboration, 2020. ) for meta-analysis and R software (R Core Team. (2024). R: A language and environment for statistical computing (Version 4.4.2) and Python (Python Software Foundation. (n.d.). Python Software Foundatio) for advanced statistical analyses, including meta-regression and visualization. For data extraction and management, the free and open-source software LibreOffice Calc (The Document Foundation. (n.d.). LibreOffice Calc (Version 7.5))was used as an alternative to proprietary spreadsheet tools. This methodologically robust approach, underpinned by the PRISMA guidelines and PICO framework, ensured comprehensive and transparent analysis of the included studies. A total of 18 studies were selected, providing valuable insights into the effectiveness of interventions and informing clinical practice and future research

Files

Files (348.2 kB)

Name Size Download all
md5:247fad5c8cccf621c017f43a46562897
274.9 kB Download
md5:dea599dffe001fd2c6a7b56b26fb098d
73.3 kB Download

Additional details

Dates

Accepted
2025-01-02
Citation Prieyadharshini Jayaprakasam, Jeyaram Nadarajan Saraswathy. Psychological Impact of Pregnancy Loss and the Effectiveness of Interventions: A Systematic Review and Meta-Analysis. PROSPERO 2025 CRD42025635112 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42025635112

Software

Repository URL
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42025635112

References

  • 1. Song, J. Y., Dong, F. Y., Li, L., Zhang, X. X., Wang, A. J., Zhang, Y., Gao, D. D., Xiao, J. M., & Sun, Z. G. (2021). Immediate versus delayed frozen embryo transfer in women following a failed IVF-ET attempt: A multicenter randomized controlled trial. Reproductive Biology and Endocrinology, 19(1), 131. https://doi.org/10.1186/s12958-021-00819-9 2. Saupstad, M., Bergenheim, S. J., Bogstad, J. W., Petersen, M. R., Klajnbard, A., Prætorius, L., Freiesleben, N. I. C., Englund, A. L., Løkkegaard, E. C. L., Knudsen, U. B., Husth, M., Alsbjerg, B., Møller, J. E., Dam, T. V., Forman, J. L., Pinborg, A., & Løssl, K. (2024). Progesterone concentrations on blastocyst transfer day in modified natural cycle frozen embryo transfer cycles. Reproductive BioMedicine Online, 49(1), 103862. https://doi.org/10.1016/j.rbmo.2024.103862 3. Diop, A., Abbas, D. F., Ngoc, N. T. N., Martin, R., Razafi, A., Tuyet, H. T. D., & Winikoff, B. (2020). A double-blind, randomized controlled trial to explore oral tranexamic acid as an adjunct for the treatment of postpartum hemorrhage. Reproductive Health, 17(34). https://doi.org/10.1186/s12978-020-0887-2 4. Abbas, D. F., Mirzazada, S., Durocher, J., Pamiri, S., Byrne, M. E., & Winikoff, B. (2020). Testing a home-based model of care using misoprostol for prevention and treatment of postpartum hemorrhage: Results from a randomized placebo-controlled trial conducted in Badakhshan province, Afghanistan. Reproductive Health, 17(88). https://doi.org/10.1186/s12978-020-00933-8 5. Zhou, M., Guo, J. Y., Li, T. Y., Zhou, C. H., Zhang, X. Q., Wei, W., Zhou, J., Redding, S. R., Ouyang, Y. Q., & Chen, H. J. (2024). Effect of early essential newborn care on breastfeeding and outcomes of mothers/newborns post-cesarean section: A randomized controlled trial in China. Reproductive Health, 21(183). https://doi.org/10.1186/s12978-024-01932-9 6. Pantos, K., Simopoulou, M., Maziotis, E., Rapani, A., Grigoriadis, S., Tsioulou, P., Giannelou, P., Nitsos, N., Tzonis, P., Koutsilieris, M., & Sfakianoudis, K. (2021). Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: A randomized pilot study. Scientific Reports, 11(1), 15581. https://doi.org/10.1038/s41598-021-95072-w 7. Sonalkar, S., Koelper, N., Creinin, M. D., Atrio, J. M., Sammel, M. D., McAllister, A., & Schreiber, C. A. (2020). Management of early pregnancy loss with mifepristone and misoprostol: Clinical predictors of success from a randomized trial. American Journal of Obstetrics and Gynecology, 223(4), 551.e1-551.e7. https://doi.org/10.1016/j.ajog.2020.04.006 8. Grantz, K. L., Elmi, A., Pugh, S. J., Catov, J., Sjaarda, L., & Albert, P. S. (2020). Maternal serum lipid trajectories and association with pregnancy loss and length of gestation. American Journal of Perinatology, 37(9), 914-923. https://doi.org/10.1055/s-0039-1689000 9. Naimi, A. I., Perkins, N. J., Sjaarda, L. A., Mumford, S. L., Platt, R. W., Silver, R. M., & Schisterman, E. F. (2021). The effect of preconception-initiated low-dose aspirin on hCG pregnancy, pregnancy loss, and live birth: Per-protocol analysis of a randomized trial. Annals of Internal Medicine, 174(5), 595–601. https://doi.org/10.7326/M20-0469 10. Lund, C., Schneider, M., Garman, E. C., Davies, T., Munodawafa, M., Honikman, S., Bhana, A., Bass, J., Bolton, P., Dewey, M., Joska, J., Kagee, A., Myer, L., Petersen, I., Prince, M., Stein, D. J., Tabana, H., Thornicroft, G., Tomlinson, M., Hanlon, C., & Susser, E. (2020). Task-sharing of psychological treatment for antenatal depression in Khayelitsha, South Africa: Effects on antenatal and postnatal outcomes in an individual randomized controlled trial. Behavior Research and Therapy, 130, 103466. https://doi.org/10.1016/j.brat.2019.103466 11. Jensen, K. H. K., Krog, M. C., Koert, E., Hedegaard, S., Chonovitsch, M., Schmidt, L., Kolte, A. M., & Nielsen, H. S. (2021). Meditation and mindfulness reduce perceived stress in women with recurrent pregnancy loss: A randomized controlled trial. Reproductive BioMedicine Online, 43(2), 246-248. https://doi.org/10.1016/j.rbmo.2021.04.018 12. Zahmatkesh, M., Faal Siahkal, S., Alahverdi, F., Tahmasebi, G., & Ebrahimi, E. (2024). The role of art therapy on quality of life of women with recent pregnancy loss: A randomized clinical trial. PLoS ONE, 19(7), e0305403. https://doi.org/10.1371/journal.pone.0305403 13. Hamel, C. C., Snijders, M. P. L. M., Coppus, S. F. P. J., Vandenbussche, F. P. H. A., Braat, D. D. M., & Adang, E. M. M. (2022). Economic evaluation of a randomized controlled trial comparing mifepristone and misoprostol with misoprostol alone in the treatment of early pregnancy loss. PLoS ONE, 17(2), e0262894. https://doi.org/10.1371/journal.pone.0262894 14. Jørgensen, M. M., Bæk, R., Sloth, J., Varming, K., Christiansen, O. B., Ditlevsen, N. E., & Rajaratnam, N. (2020). Treatment with intravenous immunoglobulin increases the level of small EVs in plasma of pregnant women with recurrent pregnancy loss. Journal of Reproductive Immunology, 140, 103128. https://doi.org/10.1016/j.jri.2020.103128 15. Saupstad, M., Bergenheim, S. J., Bogstad, J. W., Petersen, M. R., Klajnbard, A., Prætorius, L., Freiesleben, N. I. C., Englund, A. L., Løkkegaard, E. C. L., Knudsen, U. B., Husth, M., Alsbjerg, B., Møller, J. E., Dam, T. V., Forman, J. L., Pinborg, A., & Løssl, K. (2024). Progesterone concentrations on blastocyst transfer day in modified natural cycle frozen embryo transfer cycles. Reproductive BioMedicine Online, 49(1), 103862. https://doi.org/10.1016/j.rbmo.2024.103862 16. Russo, L. M., Whitcomb, B. W., Freeman, J. R., Mumford, S. L., Sjaarda, L. A., Perkins, N. J., Schliep, K. C., Grewal, J., Silver, R. M., & Schisterman, E. F. (2020). Physical activity and incidence of subclinical and clinical pregnancy loss: A secondary analysis in the effects of aspirin in gestation and reproduction randomized trial. Fertility and Sterility, 113(3), 601-608. https://doi.org/10.1016/j.fertnstert.2019.10.027 17. Lund, C., Schneider, M., Garman, E. C., Davies, T., Munodawafa, M., Honikman, S., Bhana, A., Bass, J., Bolton, P., Dewey, M., Joska, J., Kagee, A., Myer, L., Petersen, I., Prince, M., Stein, D. J., Tabana, H., Thornicroft, G., Tomlinson, M., Hanlon, C., & Susser, E. (2020). Task-sharing of psychological treatment for antenatal depression in Khayelitsha, South Africa: Effects on antenatal and postnatal outcomes in an individual randomized controlled trial. Behavior Research and Therapy, 130, 103466. https://doi.org/10.1016/j.brat.2019.103466 18. Grantz, K. L., Elmi, A., Pugh, S. J., Catov, J., Sjaarda, L., & Albert, P. S. (2020). Maternal serum lipid trajectories and association with pregnancy loss and length of gestation. American Journal of Perinatology, 37(9), 914-923. https://doi.org/10.1055/s-0039-1689000