By: Kimberly Miller
Editor’s Note: Kimberly Miller was in her fourth year of medical school when she enrolled in the FACTS elective and summarized this systematic review by Harjee et al. [1] The authors reviewed the existing literature on the surgical management of isthmoceles among patients with secondary infertility presumptively due to the isthmocele. The article was published in 2021 in the Journal of Minimally Invasive Gynecology and titled, “Reproductive Outcomes Following Surgical Management for Isthmoceles: A Systematic Review.” Although isthmoceles usually result from a cesarean section, other surgeries may lead to a small number of these scar defects as well.
Introduction
Isthmoceles are a discontinuity in the lower anterior endometrial and myometrial uterine layers usually developed following a cesarean section (C-section). [2] [3] They were first described by analyzing hysterectomy specimens from women with prior lower segment cesarean incision. The estimated incidence of isthmoceles following a C-section is 15%. These cesarean scar defects in the uterine wall may cause abnormal uterine bleeding, pelvic pain, and/or secondary infertility. [3]
“Isthmoceles are a discontinuity in the lower anterior endometrial and myometrial uterine layers usually developed following a cesarean section (C-section).”
Although the exact mechanism behind this cause of secondary infertility is unknown, it is theorized that this uterine defect allows blood to persist in the cervix, which can alter cervical mucus quality, hinder sperm transport or affect sperm quality. [4][5][6] Specifically, the bleeding from the isthmocele retained in the uterine cavity can be embryotoxic; it can lead to fluid and inflammation, decreasing the endometrium’s ability to receive embryonic implantation, and hindering sperm motility. [5][7]
“Although the exact mechanism behind this cause of secondary infertility is unknown, it is theorized that … the bleeding from the isthmocele retained in the uterine cavity … can lead to fluid and inflammation, decreasing the endometrium’s ability to receive embryonic implantation, and hindering sperm motility.”
The most common surgical treatment utilizes hysteroscopy. In this surgical approach, the cervix is dilated, the uterus is distended, and the scar is resected systematically using cautery down to bleeding muscle. This approach results in minimal adverse outcomes.
Methodology
In 2020, the authors used the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to perform a systematic literature search through MEDLINE, EMBASE, and Cochrane Library. Covidence was used to eliminate duplicates. Two independent reviewers also screened articles prior to the full analysis. Risk of bias was assessed using the Institute of Health Economics quality appraisal checklist for case series studies.
Results
A total of 13 studies were reviewed, including a randomized control trial, 6 prospective case series, and 6 retrospective case studies. A total of 234 patients underwent surgical management of an isthmocele. Eight studies used hysteroscopy, one used laparoscopy, one used either hysteroscopy or laparoscopy, and one used laparotomy or vaginal approach.
Of the 13 studies, 10 reported pregnancy outcomes. After surgical management of the isthmocele, 116 pregnancies occurred. Of these 116 pregnancies, 101 resulted in live births (87%). Of these live births, 90 (89%) were delivered by cesarean section. The articles that presented these data did not indicate the reasoning for choosing a cesarean section.
“After surgical management of the isthmocele, 116 pregnancies occurred. Of these 116 pregnancies, 101 resulted in live births (87%).”
The results of this systematic review suggest the surgical treatment of isthmoceles through hysteroscopy may be effective in treating isthmocele-associated secondary infertility. The most common source for this is the one randomized control study that only used hysteroscopy to surgically correct the isthmocele.
For an isthmocele to be resected via hysteroscopy, it must be ≥ 2.5 mm; those measuring < 2.5 mm can be surgically repaired through laparoscopy, laparotomy or a vaginal approach. Based on these surgical criteria alone, there may be surgical technical difficulties depending on the size of the isthmocele. The technical challenge alone may cause a discrepancy in outcomes of this procedure.
A meta-analysis could not be performed due to a lack of standardization in reporting pregnancies and live births as outcomes following surgical intervention. Additionally, there was insufficient data about the cause of infertility in each patient, and the articles did not mention if all other causes of infertility were excluded. There was no mention of the definition of infertility being used or whether these couples used fertility awareness-based methods (FABMs) or reproductive endocrinology and infertility (REI) methods to achieve pregnancy before or after surgical treatment for the isthmocele.
Discussion
This systematic review offers valuable insights into the lack of information about isthmocele-associated secondary infertility — from the proposed mechanism of infertility to the lack of research surrounding its repair. The authors’ goal was to assess pregnancy rates after surgical interventions to treat isthmocele-associated secondary infertility. The current evidence suggests that for women with isthmocele-associated secondary infertility and an isthmocele measuring ≥ 2.5 mm via ultrasonography, hysteroscopic surgical management can improve fertility outcomes.
“The current evidence suggests that for women with isthmocele-associated secondary infertility and an isthmocele measuring ≥ 2.5 mm via ultrasonography, hysteroscopic surgical management can improve fertility outcomes.”
Isthmoceles are just one of the many causes of infertility. It is important to always evaluate patients for structural causes of infertility, most commonly via transvaginal ultrasonography. Many structural causes of infertility can be surgically corrected, helping to restore fertility. However, it is possible and common to have more than one factor contributing to infertility. This emphasizes the importance of evaluating patients for both structural and hormonal causes of infertility to give them the best chance at achieving pregnancy if that is their desire.
References
[1] Harjee R, Khinda J, Bedaiwy MA. Reproductive Outcomes Following Surgical Management for Isthmoceles: A Systematic Review. J Minimal Invasive Gynecol. 2021;28:1291-1302.
[2]Thurmond AS, Harvey WJ, Smith SA. Cesarean section scar as a cause of abnormal vaginal bleeding: diagnosis by sonography. J Ultrasound Med. 1999;18:13-16.
[3] Morris H. Surgical pathology of the lower uterine segment cesarean section scar: is the scare a source of clinical symptoms? Int J Gynecol Pathol. 1995;14:16-20.
[4] Florio P, Fillppeschi M. Moncinic I, Marra E, Franchini M. Gubbini G. Hysteroscopic treatment of the cesarean-induced isthmocele in restoring infertility. Curr Opin Gynecol. 2012;24:180-186.
[5] Allomuvor GF, Xue M, Zhu X, Xu D. The definition aetiology, presentation, diagnosis and management of previous cesarean scar defects. J Obstet 2013;337:759-763.
[6] Tulandi T, Cohen A. Emerging manifestations of Cesarean scar defect in reproductive age women. J Minim Invasive Gynecol. 2016;23:893-902.
[7] Tanimura S. Funamoto H, Hosono T, et al. New diagnostic criteria and operative strategy for cesarean scar syndrome: endoscopic repair for secondary infertility caused by cesarean scar defect. J Obstet Gynecol Res. 2015;41:1363-1369.
ABOUT THE AUTHOR
Kimberly Miller
Kimberly Miller is a fourth-year medical student at Des Moines University School of Osteopathic Medicine in Des Moines, IA. She completed her undergraduate education at the University of Iowa in Iowa City, IA. She is interested in women’s health and hopes to empower her patients throughout their health journeys.
She enrolled in the FACTS elective to gain a better understanding of natural family planning methods and how they can help women understand their physiology. She hopes to continue to learn about these methods to offer them as options to future patients.
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