Revitalizing reproductive health: innovations and future frontiers in restorative medicine

Francesco Maria Bulletti; Evaldo Giacomucci; Maurizio Guido; Antonio Palagiano; Maria Elisabetta Coccia; Carlo Bulletti

doi:10.1177/26334941251345844

Infertility · Uterine Factor

Revitalizing reproductive health: innovations and future frontiers in restorative medicine

Bulletti FM, Giacomucci E, Guido M, Palagiano A, Coccia ME, Bulletti C

Published June 21, 2025 Therapeutic advances in reproductive health, 19

DOI 10.1177/26334941251345844 PMID 40546415 PMC PMC12182620

RRM Academy Synopsis

Review links fixing uterine causes of infertility to more pregnancies

This review pulled together 145 articles on uterine and body-wide factors in women's infertility. The authors pooled no results. Fixing problems in the uterus was linked to higher pregnancy rates in the studies they summarized. They call risk of bias the main limit.

Key Findings

The authors screened an initial pool of ~25,000 studies from January 1995 to October 2024 and kept 145 articles that met their inclusion criteria.
For a uterine septum, hysteroscopic metroplasty was reported to raise clinical pregnancy to 60%–70% and cut miscarriage to 10%–15%, from rates that can approach 50% untreated.
A randomized multicenter trial cited by the review found that removing the affected tube before IVF (salpingectomy) raised pregnancy rates to 36.6%, versus 23.9% without intervention.
Antibiotic therapy for chronic endometritis was reported to reach clinical pregnancy rates of up to 61.3% versus 43.1% untreated, with miscarriage down to 2.2% from 16.0%.
Hysteroscopic removal of submucosal fibroids was reported to raise pregnancy rates by 50%–70%, and fibroid recurrence happens in up to 30% of cases.

Interpretation

The paper summarizes other studies in a narrative. It pools no results and runs no head-to-head comparison of its own. Each percentage belongs to the study behind it, and many appear as ranges. The authors name risk of bias as the major limitation, generally highest in observational studies. The search covered English-language papers and excluded male-only infertility, so the findings cover female uterine and body-wide factors. Several pregnancy figures for the same tube surgery appear in different sections.

RRM Context

The review lists diagnosable causes of infertility: septa, polyps, adhesions, fluid-filled tubes, chronic endometritis, weight and thyroid function. Restorative reproductive medicine asks the same first question: why is conception not happening? The authors propose pairing these corrections with IVF. IVF bypasses the underlying findings. The corrections address them, and each rests on its own studies.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Infertility affects around 17.5% of reproductive-aged individuals worldwide, posing significant personal and public health challenges. Although Medically Assisted Reproduction and Assisted Reproductive Technology (ART; e.g., in vitro fertilization) have advanced outcomes, many couples fail to conceive due to unaddressed pelvic, uterine, or systemic factors.

Objectives

We aim to (1) define the current usage of Restorative Reproduction Medicine (RRM) in clinical practice, (2) compare RRM outcomes with conventional ART, and (3) propose an integrated model of RRM plus ART for optimal fertility care.

Design

A systematic review following PRISMA guidelines was conducted (INPLASY registration no. INPLASY2024110069).

Data Sources and Methods

We searched PubMed, Scopus, and Web of Science (January 1995–October 2024), combining terms such as “restorative reproductive medicine,” “intrauterine adhesions,” “myomas,” “polyps,” “hydrosalpinx,” “endometritis,” “BMI,” “thyroid dysfunction,” “microbiome,” and “assisted reproductive technology.”

Study Eligibility Criteria

studies on uterine/systemic factors affecting infertility, focusing on surgical/pharmacological RRM interventions and ART limitations.

Exclusion Criteria

male-only infertility, case reports, narrative reviews, non-English publications. Quality assessment employed the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool. We also briefly noted potential publication bias due to language and study-type restrictions.

Results

From >25,000 initial titles, 3 sequential screenings yielded 145 key articles addressing uterine (septum, myomas, polyps, adhesions) and systemic (body mass index (BMI) extremes, thyroid dysfunction, microbiome imbalance) factors. Surgical corrections (e.g., hysteroscopic removal of polyps/myomas, salpingectomy for hydrosalpinx) significantly improved natural conception and ART success (⩾20%–40% increase in clinical pregnancy). Chronic endometritis treatment, endometrial microbiome modulation, and BMI/thyroid optimization further improved pregnancy rates by 15%–20%. Comparisons of RRM versus ART alone indicated that RRM often lowers overall cost and may reduce miscarriage, while ART offers immediate embryo transfer. Combining RRM to correct pathologies prior to ART can boost implantation and live birth rates (⩾40%–70% improvement in some studies).

Conclusion

Restorative Reproductive Medicine comprehensively addresses pelvic and systemic abnormalities, thereby enhancing fertility outcomes and complementing ART. A proposed integrated model—RRM diagnostics/interventions followed by ART if needed—maximizes success, reduces time/cost, and emphasizes holistic reproductive health. Further multicenter trials are warranted to standardize protocols and fully realize RRM’s potential in modern fertility care.

Topics

Infertility › Uterine Factor › Fibroids and Polyps · Restorative Reproductive Medicine › Restorative Care and Assisted Reproduction › Outcome Comparisons · Reproductive Surgery › Uterine Surgery › Myomectomy

Francesco Maria Bulletti, Evaldo Giacomucci, Maurizio Guido, Antonio Palagiano, Maria Elisabetta Coccia, Carlo Bulletti

F Bulletti, E Giacomucci, M Guido, A Palagiano, M Coccia, C Bulletti

PMID 40546415 40546415 DOI 10.1177/26334941251345844 10.1177/26334941251345844 Bulletti et al. 2025, Bulletti 2025

Revitalizing reproductive health: innovations and future frontiers in restorative medicine

Review links fixing uterine causes of infertility to more pregnancies

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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