Fibroids and natural fertility: a systematic review and meta-analysis

Somigliana, Edgardo; Reschini, Marco; Bonanni, Valentina; Busnelli, Andrea; Piani, Letizia Li; Vercellini, Paolo

doi:10.1016/j.rbmo.2021.03.013

Cited by 31 publications

(12 citation statements)

References 58 publications

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“…at increased risk of a range of pregnancy-related adverse events (124). Such variability in the clinical manifestations of fibroids, including a majority of asymptomatic patients, may be related to the fact that fibroids are a heterogeneous condition with huge differences among affected women in terms of the number, dimensions, and location of the lesions and the concomitant presence of conditions that can interfere with fertility (125). Uterine and endometrial sparing surgical interventions are therapeutic options available to women with severe fibroid-associated symptoms who are planning on becoming pregnant.…”

Section: Surgery Is Mandatory: Place Of Minilaparotomy/ Laparotomymentioning

confidence: 99%

“…Indeed, the effect of intramural fibroids on fertility remains controversial. On the one hand, there is evidence that fibroids may reduce both natural fertility (125) and ART-induced chances of live birth (129,130); on the other hand, it is uncertain whether myomectomy improves the postoperative clinical pregnancy rate in case of intramural fibroids (130). The substantial heterogeneity of the disease itself and the existence of several confounding factors, such as age, associated diseases, and fertility factors, may explain such inconsistency.…”

Section: Surgery Is Mandatory: Place Of Minilaparotomy/ Laparotomymentioning

confidence: 99%

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Intramural myomas more than 3–4 centimeters should be surgically removed before in vitro fertilization

Dolmans

Isaacson

Zhang

et al. 2021

Fertility and Sterility

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Section: Surgery Is Mandatory: Place Of Minilaparotomy/ Laparotomymentioning

confidence: 99%

Section: Surgery Is Mandatory: Place Of Minilaparotomy/ Laparotomymentioning

confidence: 99%

Intramural myomas more than 3–4 centimeters should be surgically removed before in vitro fertilization

Dolmans

Isaacson

Zhang

et al. 2021

Fertility and Sterility

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“…Although mostly benign, severe symptoms develop in 15–30% of patients; irregular, prolonged, or heavy vaginal bleeding are the most common manifestation frequently associated with anemia [ 1 ]. In addition, leiomyomas may interfere with natural and in vitro fertility and increase the risk of adverse pregnancy outcomes [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Stem Cell Growth and Differentiation in Organ Culture: New Insights for Uterine Fibroid Treatment

et al. 2022

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Organ culture allows for the understanding of normal and tumor cell biology, and tissues generally remain viable for 5–7 days. Strikingly, we determined that myometrial and MED12 mutant leiomyoma cells repopulated cell-depleted tissue slices after 20 days of culture. Using immunofluorescence and quantitative PCR of stem cell and undifferentiated cell markers, we observed clusters of CD49b+ cells in tumor slices. CD49b+ cells, however, were sparsely detected in the myometrial slices. Almost all LM cells strongly expressed Ki67, while only a few myometrial cells were stained for this proliferation marker. The CD73 marker was expressed only in tumor cells, whereas the mesenchymal stem cell receptor KIT was detected only in normal cells. HMGA2 and CD24 showed broader expression patterns and higher signal intensity in leiomyoma than in myometrial cells. In this study, we propose that activating CD49b+ stem cells in myometrium leads to asymmetrical division, giving rise to transit-amplifying KIT+ cells that differentiate to smooth muscle cells. On the contrary, activated leiomyoma CD49b+ cells symmetrically divide to form clusters of stem cells that divide and differentiate to smooth muscle cells without losing proliferation ability. In conclusion, normal and mutant stem cells can proliferate and differentiate in long-term organ culture, constituting a helpful platform for novel therapeutic discovery.

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“…The relation between fibroids and infertility remains controversial. There is a long-lasting consensus that submucosal lesions are detrimental but, for intramural and subserosal lesions, their impact is yet unclear ( Somigliana et al , 2007 ; Hur et al , 2019 ; Metwally et al , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence from IVF studies suggests a detrimental effect of submucosal and intramural but not subserosal lesions. According to the most recent meta-analyses on this subject, the corresponding odds ratios (ORs) of live birth were 0.3 (95% CI: 0.1–0.8), 0.6 (95% CI: 0.5–0.7) and 1.0 (95% CI: 0.7–1.5), respectively ( Somigliana et al , 2007 ; Pritts et al , 2009 ; Rikhraj et al , 2020 ). On the other hand, evidence from IVF cannot be considered exhaustive.…”

Section: Introductionmentioning

confidence: 99%

The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case–control study

Bonanni

Reschini

Vecchia

et al. 2022

Human Reproduction Open

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STUDY QUESTION Do small and asymptomatic intramural and subserosal uterine fibroids affect female fertility? SUMMARY ANSWER Small and asymptomatic fibroids that do not encroach the endometrial cavity appear to not markedly affect female fertility. WHAT IS KNOWN ALREADY The available evidence on uterine fibroids and fertility is limited. Most information has been obtained in IVF settings by comparing the success in women affected and not affected by fibroids. These studies have shown a detrimental effect of submucosal and possibly intramural fibroids. However, this study design provides information only on embryo implantation, not on female fertility in general. STUDY DESIGN, SIZE, DURATION A retrospective observational case-control study on 200 women whose partner was diagnosed with severe male infertility and 200 women with unexplained infertility was conducted. If the null hypothesis (that fibroids do not affect fertility) is valid, one would expect a similar prevalence of fibroids in the two study groups. Conversely, if fibroids do impact fertility, one would expect a higher prevalence among women with unexplained infertility. The study was carried out at the Infertility Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico covering a 5-year period between January 2014 and June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS We retrospectively recruited women seeking pregnancy whose partner was repeatedly documented to have a sperm concentration below 1 million/ml and matched them by age and study period to a group of women with unexplained infertility. The latter group of women were considered as cases (infertile subjects) while the former group of women were considered as controls (reflecting the general female population). Women with fibroids could be included in both study groups; only those with submucosal lesions were excluded. MAIN RESULTS AND THE ROLE OF CHANCE Fibroids were diagnosed in 31 women (16%) with unexplained infertility and in 32 women (16%) with severe male factor infertility. The adjusted OR of carrying fibroids in women with unexplained infertility was 0.91 (95%CI: 0.52 - 1.58). Subgroup analyses according to number, dimension and location of fibroids failed to highlight an increased risk of infertility in any group. LIMITATIONS, REASONS FOR CAUTION This is a retrospective study and some inaccuracies in fibroids detection cannot be ruled out. Moreover, the relatively small sample size hampers robust subgroup analyses. Even though we excluded women with patent causes of infertility, some women with specific causes of infertility could have been included among controls (yet are expected to account for less than 10% of the group). WIDER IMPLICATIONS OF THE FINDINGS This study suggests that small fibroids that do not encroach the endometrial cavity do not markedly affect female fertility. This information is clinically relevant when counselling infertile women with small fibroids and an otherwise unremarkable diagnostic work-up. Surgery may still be considered but only in selected cases. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Italian Ministry of Health: Current research IRCCS. ES reports grants from Ferring, grants and personal fees from Merck, and grants and personal fees from Theramex, outside the submitted work. All the other authors do not have any competing interest to declare. TRIAL REGISTRATION NUMBER NA

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Fibroids and natural fertility: a systematic review and meta-analysis

Abstract: He has authored or co-authored more than 330 articles in international journals.

Cited by 31 publications

References 58 publications

Intramural myomas more than 3–4 centimeters should be surgically removed before in vitro fertilization

Intramural myomas more than 3–4 centimeters should be surgically removed before in vitro fertilization

Stem Cell Growth and Differentiation in Organ Culture: New Insights for Uterine Fibroid Treatment

The impact of small and asymptomatic intramural and subserosal fibroids on female fertility: a case–control study

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