The Impact of Non Cavity Distorting Intramural Fibroids on IVF Outcomes Systematic Review and Meta Analysis

However, there has been existence of an array of problems on this topic as far as medical literature is of concern. Fibroids in the uterine cavity express heterogeneity not only in the size and frequency but also in the composition and location1. Therefore, an alteration in any of the factors could result in an eminent alteration on the effects on the fertility. Several medical meta-analytical studies have been in place in an attempt to determine how leiomyoma influences fertility and there has been a wide disparity in findings as most of the studies have registered serious flaws in methodology. The designs of the investigations have frequented poor designs. Objectives The major objective of this paper was to investigate the impact of non-cavity distorting IM with or without SS besides investigating the impact of non-cavity distorting exclusive IM fibroid.

It also aims at investigating the impact of myomectomy on reproductive outcome of women undergoing IVF. Instead of a narrative review of literature, the paper applies meta-analytic techniques. Always consistent of a standard literature review is commentary findings derived from previous studies. However, the approach of this paper depicts a qualitative character, which neither offer room for qualitative assessing of the effect of interest nor enable its stabilization for the invariant methods applicable across studies7. 1 Electronic Searches The electronic databases, trial registers, as well as websites that will attract attention for literature searches include University of Phoenix Library’s ProQuest, CINAHL, PUBMED, the Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE. Other electronic sources will include a search on Google Scholar database.

Search of Google Scholar presents results by relevance and ranking and takes into account the full text of documents10. It will be a helpful tool as it provides the source, author, and the frequency of its recent citation in publications of a common course11. An excerpt of the article is also shown with the search terms highlighted, the frequency of citation, and related articles. 2 Interventions Eligible for inclusion will be women with IM and/ or SS compared to women with no fibroids, women with exclusive IM compared to women with no fibroids, and post myomectomy women compared to women with IM and/ or SS fibroids. Factors of consideration in comparing the variables will be low birth rate (LBR), cumulative pregnancy rate (CPR), implantation rate (IR), and miscarriage rate (MR)19.

3 Outcome Measures Primary Outcomes i. Effectiveness: Live Birth Rate (LBR) defined as the number of deliveries that resulted in at least one live born baby expressed per 100 patients. ii. Subsequent to an initial screening of titles as well as abstracts obtained from the search, there will be a retrieval of a complete text of the eligible studies. Likewise, there will be an independent examination of the full text articles for any compliance with the criteria of inclusion in addition to a selection for studies, which are eligible for an inclusion in the review22. As per the requirements to the eligibility of the study, there will be a correspondence to the investigators. Resolution of disagreement to the eligibility of the study will ensue through either a discussion or a third party author review.

There will be an independent assessment of the risk of bias through the Cochrane tool for assessing risk of bias. 1 Data Synthesis In case there is a sufficient similarity shown by the studies, a combination of data will ensue using either a fixed effect model or a random effect model in the following comparisons: i. Women with IM and/ or SS compared to women with no fibroids while considering the following factors a. LBR b. CPR c. IR d. MR There will also be a graphical display of an increase in the odds of a specific outcome, which could be either beneficial as in the case of live births or detrimental in the meta-analysis to the right of the centerline whereas a decrease in the odds recorded to the left26.

3 Data Analysis 3. 0 RevMan 5. 3 There will be a review through RevMan 5. RevMan 5. Results 4. 1 Search Results Records identified through initial database screening (n=2482). Full-text articles assessed for eligibility (n=187). Studies included in data synthesis (n=58). Final studies included in meta-analysis (n=27). All the women in the intervention group had IM and/or SS fibroids, had either undergone myomectomy, or had IM and/or SS fibroids undergoing IVF iii. Outcomes 7 out of 26 studies reported IVF and ICSI. Likewise, 16 out of 26 studies exclusively reported IVF. However, only 3 out of 36 studies reported ICSI only31. 3 Excluded Studies There was an exclusion of some studies from the meta-analysis. Within the study bias, potential sources were evident in the other eight sources. 5 Comparing First and Second Objective i. Primary Outcomes Live Birth Rates The first objective (impact of IM ± SS) had an association with significantly decreased LBR in women with IM ± SS compared to women with no fibroids as shown in table 133.

Likewise, the second objective (Impact of exclusive IM fibroid) also had significantly decreased LBR in women with exclusive IM compared to women with no fibroids as shown in table 5. Adverse Events The first objective showed an association with significantly decreased CPR in women with IM ± SS compared to women with no fibroids as shown in table 2. However, the third objective showed no significant different CPR in post myomectomy women compared to women with IM & or SS fibroids as shown in table 10. ii. Secondary Outcomes Miscarriage Rate The first objective showed an association of significantly increased MR in women with IM ± SS compared to women with no fibroids as shown in table 436. However, the third objective showed no significant different MR in post myomectomy women compared to women with IM & or SS fibroids as shown in table 11.

Conclusion Systematic review as meta-analysis in evaluation of the association between non-cavity distorting IM fibroids and IVF outcome in an attempt to explore the available inconsistencies in the literature show a variety of findings. Gambadauro, Pietro. "Dealing with uterine fibroids in reproductive medicine. " Journal of Obstetrics and Gynaecology 32, no. Griffiths, A. , Arianna D’Angelo, and N. Marqueta, Belen, Pedro N. Barri, Buenaventura Coroleu, Pedro N. Barri Soldevila, and Ignacio Rodriguez. "Effect of non-cavity distorting intramural fibroids on assisted reproduction outcomes: a cohort study. " Journal of Endometriosis and Pelvic Pain Disorders 8, no. "Uterine fibroids: impact on fertility and pregnancy loss. " Obstetrics, Gynaecology & Reproductive Medicine 17. Ojo-Carons, Mary, Sunni L. Mumford, Alicia Y. Armstrong, Alan H. Sunkara, Sesh Kamal, et al. "The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis.

This is attributed to the diversity of location, size 7, number and rate of growth of UF. UF are generally associated with subfertility. 8-9Nearly 5-10% women with infertility are having one or more UF, nevertheless, following exclusion of other causes of infertility only 1-2. 4% have UF. 6-7 There is little debate regarding the impact of subserosal fibroid (SS) and submucosal fibroids (SM) on fertility. Fibroid size ranged up to 8 cm, although mean size and number were not uniformly reported. Sub analysis limited to studies with mean patient age less than 37 years, and limited to first fresh IVF cycle attempt, confirmed a negative effect of intramural fibroids on pregnancy outcomes. 9 Another meta-analysis in which only 10 studies were included just above 3000 cycles. Further they have included only 3 studies for LBR, moreover 4 for MR.

There is significant heterogeneity. Enquiries were also made regarding any studies that were specific for this field yet had not been published or were on progress. The searches were done without any limitation concerning language. Study Selection The selection was done based on articles that had their target population as women who were undertaking treatment on in vitro fertilization, either with intracytoplasmic sperm injection, or without it. Additionally, articles in which target population had intracytoplasmic sperm injection only were also included. The existence of intramural fibroids that were non-cavity distorting was the exposure among the study group. The second stage involved examining of the full manuscripts aforementioned to establish whether they met the inclusion criteria, otherwise they were excluded. Those citations that were duplicated had their publication that was either most recent or more complete selected for the review and meta-analysis.

The two reviewers used arbitration or consensus performed by a third reviewer as a method of reaching an agreement every time they disagreed. Data Collection Quality assessment of the articles was then conducted to completion by the two reviewers. This assessment was based on the Newcastle-Ottawa Scale (Wells, B. Publication bias was also assessed using funnel plot. Statistical analysis was then carried out using RevMan 5. 12 Results The initial database screening generated a total of 2482 citations. Out of this number, a total of 2,295 were excluded since they did not meet the inclusion criteria. This implies that only 187 articles had their full manuscript assessed for eligibility. In the control groups, all the studies had their control population with myomectomy but without fibroids. • Primary Outcome Live Birth Rate (LBR) Results from 16 studies in which the women undergoing IVF treatment but had both intramural and subserosal fibroids indicated a statistically significant relative reduction in live birth rate of in women with IM and SS compared to women with no fibroids.

The value of I2 was 47%. This shows that there was significant heterogeneity in LBR between all the studies. The summary was as follows: In six studies in which the participants had IM exclusively, the results indicated a statistically significant relative reduction in live birth rate in women with IM compared to women without fibroids. Results pooled from 5 studies show no significant difference in the rate of implantation between women who have IM exclusively compared to those who had no fibroids. However, the inconsistency with these studies is very high, with a percentage of 81%, as shown below. Miscarriage Rate Miscarriage significantly increased in women with IM with or without subserosal fibroids compared to the women who had no fibroids after undertaking in vitro fertilization treatment in 20 of the studies.

The I2 value was 21% indicating a little inconsistency in the pooled studies. In 9 studies, women with IM exclusively showed a statistically significant increase in the rates of miscarriages compared to those who had no fibroids. The secondary outcome of implantation rate was only determined in ten of the reviewed studies. The results indicate that the participants did not show any variation, between women with fibroids and those without, that is statistically significant. The implication of this is that intramural fibroids with or without subserosal fibroids does not significantly affect implantation following in vitro fertilization. Just like live birth rates and clinical birth rates, the number of women with non-cavity distorting intramural fibroids, with or without subserosal fibroids, who experienced miscarriages were significantly higher compared to women who had no fibroids when both were subjected to in vitro fertilization treatment.

Unlike the other outcomes in which inconsistencies were high, the studies that were pooled for miscarriage showed almost negligible inconsistencies. The data used for this review was from observational studies. It was heterogenous and as such requires caution when interpreting. While IM fibroid may impact negatively on IVF, myomectomy is only recommended for patients in whom IVF has failed. However, there is no sufficient evidence to back the success of myomectomy in failed IVF. Finally, further random controlled trials including those of myomectomy should be done to avail scientific evidence. " American family physician 75. Brady, Paula C. , Aleksandar K. Stanic, and Aaron K. Styer. "Clinical presentation of fibroids. " Best practice & research Clinical obstetrics & gynaecology 22. Griffiths, A. , Arianna D’Angelo, and N. Amso.

L. -L. Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review. Human Reproduction, 852-863. Cochrane Community. W. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril, 1215-1223. Stovall DW, Parrish SB, Van Voorhis BJ, Hahn SJ, Sparks AE, Syrop CH. Uterine leiomyomas reduce the efficacy of assisted reproduction cycles: results of a matched follow-up study. Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment. Fertil Steril 1998; 70: 687–691. Dietterich C, Check JH, Choe JK, Nazari A, Fox F. The presence of small uterine fibroids not distorting the endometrial cavity does not adversely affect conception outcome following embryo transfer in older recipients. Clin Exp Obstet Gynecol 2000; 27: 168–170.

Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilisation-intracytoplasmic sperminjection. Fertil Steril 2004;81:582–587. Oliveira FG, Abdelmassih VG, Diamond MP, Dozortsev D, Melo NR, Abdelmassih R. Small uterine fibroids did not negatively affect the success of infertility treatment with intracytoplasmic sperm injection. Evidence based Obstet Gynecol 2005; 7: 31–32. The effect of fibroids without cavity involvement on ART outcomes independent of ovarian age. Hum Reprod 2007;22:521–526. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:719–748. Endometrial receptivity and implantation are not affected by the presence of uterine intramural leiomyomas: a clinical and functional genomics analysis. J Clin Endocrinol Metab 2008;93:3490–3498. Vimercati A, Scioscia M, Lorusso F, Laera AF, Lamanna G, Coluccia A, Bettocchi S, Selvaggi L, Depalo R.

Do uterine fibroids affect IVF outcomes? Reprod Biomed Online 2007;15:686–691. Bozdag G, Esinier I, Boynukalin K, Aksu Gunalp S, Gutgan T. JAMA 1999;282:1083–1085. Guven, S. , Kart, C. , Unsal, M. A. Effects of the distance between small intramural uterine fibroids and the endometrium on the pregnancy outcomes of in vitro fertilization-embryo transfer. Gynecol Obstet Invest, 62-68. Yan, L. , L, D. , C, L. Hum Reprod 2001; 16: 2411–2417. Healy DL. Impact of uterine fibroids on ART outcome. Environ Health Perspect 2000;108(Suppl. Higgins JPT, Thompson SG. C. Fertility outcomes following myomectomy in an urban hospital setting. J. Natl. Med. Fertil. Steril. Surrey, E. S. , Lietz, A. , Lurie, D. Effect of fibroids on cumulative probability of pregnancy in women taking follicle maturing drugs without assisted reproductive technology. Clin. Exp. Obstet.