Effectiveness of Reproductive Surgery in Infertility: A Review of Research
By: Kirsten Linnartz, MD
Director’s Note: With infertility and reproductive health issues on the rise, physicians and other medical professionals continue to search for the best options for their patients. In recent years, a trend has emerged among doctors, with fewer turning to surgery when caring for these patients. Former FACTS elective student, Dr. Kirsten Linnartz, was intrigued by this shift in medical care and summarized a study comparing surgery versus assisted reproductive technology (ART) for infertility, polycystic ovary syndrome (PCOS), and several other common fertility issues. The study, published in 2010 by Bosteels et al, is titled, “The Effectiveness of Reproductive Surgery in the Treatment of Female Infertility: Facts, Views, and Vision.” To learn more about these and other common women’s health conditions that can be treated with a restorative reproductive medicine approach, sign up for our online CME course here!
Introduction
Surgery to address infertility is becoming less common, and assisted reproductive technology (ART) is taking the mainstage. [1] While the exact reason for this shift is unknown, contributing factors may include risks of surgery, lack of surgical expertise, and the desire to achieve pregnancy without delay. [2] The limited research available to affirm the effectiveness of hysteroscopy and diagnostic laparoscopy in infertility may also play a role. [1] [3] [4] The purpose of the systematic review published in 2010 by Bosteels et al was to examine the effectiveness of surgical interventions in women with subfertility by reviewing randomized controlled trials (RCTs) measuring pregnancies and live births. [2]
Methodology
RCTs from MEDLINE, EMBASE, and Cochrane Library were extracted for the systematic review and two researchers completed the study selections. [2] Any unclear methods or procedures were clarified with authors of the RCTs. The Dutch Cochrane Centre was utilized for quality assessment of the studies. Overall, studies were evaluated on randomization methods, allocation concealment, blinding, and assessment of the data. [2] Statistical analysis was conducted using RevMan5 with the Mantel-Haenszel fixed effects model to express risk ratios. [2] The number needed-to-treat was calculated, and bias was estimated using the Cochrane Collaboration software.
Results
Upon review, 63 articles were included in the meta-analysis. Results were presented as subtopics to address the question, “How effective is reproductive surgery by laparoscopy in subfertile women compared to alternative treatments?” [2]
Evaluating patients with endometriosis
In two studies of women with minimal or mild endometriosis, there was a statistically significant benefit in undergoing laparoscopic treatment to increase the ongoing pregnancy or live birth rate as compared to expectant management, in patients with and without endometriotic adhesions (RR 1.5, 95% CI 1-2.1). [2] [5] [6] In patients with moderate-to-severe endometriosis with endometriotic cysts, two published trials presented superior results in achieving conception at 1 year with cyst excision versus ablation technique (RR 2.8). [7] [8] Furthermore, the number needed-to-treat (NNT) was 3 when comparing laparoscopic excision to ablation and fenestration. [2] No studies assessed treatment methods in deeply infiltrative endometriosis.
“In two studies of women with minimal or mild endometriosis, there was a statistically significant benefit in undergoing laparoscopic treatment to increase the ongoing pregnancy or live birth rate as compared to expectant management, in patients with and without endometriotic adhesions.”
Considering ovarian diathermy in PCOS
For patients with clomiphene-resistant PCOS, when comparing ongoing pregnancy rates with gonadotropin treatment vs. laparoscopic ovarian diathermy (LOD) plus or minus clomiphene citrate, there was no difference between the treatment strategies (RR 1). [9-14] However, there were fewer multiple pregnancies in the laparoscopic group compared to the gonadotropin group (RR 0.16). [2] Furthermore, for every 6 couples treated with LOD, one less multiple pregnancy is expected when compared to gonadotropin treatment.
Considering tubal factors of infertility
When addressing a hydrosalpinx, the meta-analysis concludes that surgical treatment resulted in a treatment effect 1.9 times that of expectant management. [2] In this situation, for every 7 women treated with surgical management, 1 additional pregnancy results when compared to immediate IVF treatment. [2]
In case of adhesions, intrauterine adhesions, and intrauterine septa
The systematic review did not find any relevant RCTs or enough information to draw conclusions about adhesions. [2]
Evaluating patients with intramural, subserosal or submucosal fibroids
Upon review of one RCT that addressed treatment of patients with intramural and subserosal fibroids, there was no statistically significant difference in pregnancy outcome when comparing surgery to expectant management. However, there was a trend toward improving rate of pregnancy after 1 year (RR 1.2). [2] [15] When addressing submucosal fibroids, the article concludes a hysteroscopic myomectomy doubles pregnancy rate when compared to nonsurgical management, with a NNT of 3. [2] [15] [16]
Treating a patient with intrauterine polyps
Surgical polypectomy is advised, as removing polyps doubles rates of pregnancy. [17]
Managing patients with recurrent IVF failure
RCTs found that hysteroscopy increases pregnancy rate by close to 2 times in infertile patients with two or more failed IVF attempts prior to more IVF cycles with a NNT of 7. [2] [19-21] Yet, there was no benefit of diagnostic laparoscopy prior to IUI treatment (RR 0.89). [2] [18]
“RCTs found that hysteroscopy increases pregnancy rate by close to 2 times in infertile patients with two or more failed IVF attempts prior to more IVF cycles with a number needed-to-treat of 7.”
Discussion
Evaluating patients with endometriosis
Laparoscopic treatment of mild or minimal endometriosis is “likely beneficial” for patients, though there are conflicting studies. [2] In the RCTs evaluated, atypical endometrial lesions were not accounted for and should be addressed in future studies. [2] Excising endometrial cysts is preferred to drainage when it comes to pregnancy rate. Unfortunately, a potential side effect of this method is accidental excision of ovarian tissue, leading to decreased ovarian volume and potentially decreased ovarian reserve long term. [22] [23] Patients should be made aware that some treatments to address underlying causes of infertility could incidentally cause fertility struggles down the line. The FACTS elective, Fertility Awareness in Women’s Health, teaches early on that surgery for endometriosis is recommended by physicians who are helping couples struggling with infertility.
Considering ovarian diathermy in PCOS
In patients with clomiphene-resistant PCOS, LOD can achieve equal pregnancy rates as gonadotropins through follicular recruitment and ovulation, but LOD can also cause long-term side effects. There is a possibility for adhesions, which may or may not have clinical implications such as premature ovarian failure. [2] During an online shadowing experience as part of the FACTS elective, I learned another component of dealing with PCOS is optimizing different patient factors to maximize the likelihood of pregnancy (i.e., controlling insulin and blood glucose levels, regulating BMI, and encouraging adherence to medications).
Considering tubal factors of infertility
In patients with hydrosalpinx, there is good evidence to suggest surgical treatment of the hydrosalpinx prior to IVF will double pregnancy rates. [2] The fluid within a hydrosalpinx is toxic to the uterine cavity and endometrium. [2] While a salpingectomy removes the hydrosalpinx, salpingectomies affect ovarian reserve by promoting greater baseline FSH and decreased ovarian response. [24] The effect on pregnancy outcomes is uncertain and should be addressed in future RCTs. Other options to treat hydrosalpinx include occlusion, needle aspiration or expectant management. [2] More RCTs need to be conducted on IVF and different hydrosalpinx treatments, including expectant management.
Evaluating patients with intramural, subserosal or submucosal fibroids
The role of fibroids in infertility is still debated. Fibroids disrupt the transport and implantation of the egg as well as the sperm’s ability to reach the egg. [2] They may cause local inflammation, endometritis, and abnormal vasculature and contractility. [2] While it’s been taught that submucosal fibroids have the greatest effect on fertility, some scholars argue that fibroid size, number, and physical distortion of the uterine cavity are more important than fibroid layer location. [25] Nevertheless, studies have shown hysteroscopic removal of submucosal fibroids doubles pregnancy rates. [2]
Treating a patient with intrauterine polyps
Though one RCT discussed the benefit of polypectomies to promote pregnancy, not everyone with a polyp should be recommended for surgery. [2] [26] The location and number of polyps is meaningful and should be taken into account before recommending surgery.
The study by Bosteels et al has many strengths. It was a meta-analysis of multiple RCTs, which in theory is less biased compared to other study designs. The study also assessed biases of previously published papers, which calls into question some of the statistics we have previously learned about effectiveness of surgical treatment strategies; only 50% of the RCTs had adequate allocation concealment, and only 20% had adequate blinding. [2] The article also avoided generalizing while ensuring readers understood there were caveats to each situation. Just because a patient has a certain disease does not mean his or her treatment looks exactly like others with the same condition.
Limitations of the article include a confusing introduction that seemed to discourage fertility surgery while much of the evidence later presented did advocate for surgery. The authors were also aware of possible detection bias, as some of them previously published a paper on this topic, and the limitation of not including certain MeSH terms (endometriosis, fibroids, polyps, tubal pathology), which may have excluded some studies from their analysis. [2]
This article is relevant to women’s health, family planning, and fertility awareness. It is important to know the fertility options offered to patients are grounded in research with multiple RCTs and meta-analyses to confirm benefits. The workup for infertility should take each of these situations into account, from pursuing pelvic imaging to tracking ovulation and reviewing lab work to assess for hormonal abnormalities or PCOS. Fertility tracking used in conjunction with surgery encourages women to seek the source of their infertility and treat the underlying cause, rather than resorting immediately to expensive IUI or IVF, which was discussed at length in the FACTS course.
“Fertility tracking used in conjunction with surgery encourages women to seek the source of their infertility and treat the underlying issue, rather than resorting immediately to expensive IUI or IVF.”
Conclusion
Reproductive surgery may restore an optimal environment for pregnancy; however, risks and effectiveness of specific surgeries should be considered when counseling patients with infertility, especially when some of these remedies may have long-term side effects. Future research needs to be done on the long-term effects of surgical interventions, especially if the benefits of pregnancy are only seen immediately, with decline in the future. Furthermore, more research is needed on the benefits or risks of treating adhesions, intrauterine adhesions, and intrauterine septa prior to IUI or IVF. [2]
References
[1] Bosteels J, van Herendael B, Weyers S et al. The position of diagnostic laparoscopy in current fertility practice. Hum Reprod Update. 2007;13:477-85.
[2] Bosteels J, Weyers S, Mathieu C, Willem Mol B, D’Hooghe T. The effectiveness of reproductive surgery in the treatment of female fertility: facts, views, and vision. F,V, &V in ObGYN. 2010,2(4):00-00.
[3] Forman RG, Robinson JN, Mehta Z et al. Patient history as a simple predictor of pelvic pathology in subfertile women.Hum Reprod. 1993;8:53-5.
[4] Collins A, Burrows EA, Willan AR. The prognosis for live birth among untreated infertile couples. Fertil Steril. 1995;64:22-8.
[5] Marcoux S, Maheux R, Bérubé S et al. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med. 1997;337:217-22.
[6] Gruppo Italiano per lo Studio dell’Endometriosi. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomised trial. Hum Reprod. 1999;14:1332-4.
[7] Alborzi S, Momtahan M, Parsanezhad ME et al. A prospective randomised study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas. Fertil Steril. 2004;82:1633-7.
[8] Beretta P, Franchi M, Ghezzi F et al. Randomised clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril. 1998;70:1176-80.
[9] Bayram N, van Wely M, Bossuyt P et al. Randomised clinical trial of laparoscopic electrocoagulation of the ovaries versus recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome. Abstract 0-148 of the 17th Annual Meeting of the ESHRE. 2001, Lausanne, Switzerland.
[10] Farquhar CM, Williamson K, Gudex G et al. A randomised controlled trial of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene-resistant polycystic ovarian syndrome. Fertil Steril. 2002;78:404-11.
[11] Ghafarnegad M, Arjmand N, Khazaeipour Z. Pregnancy rate of gonadotrophin therapy and laparoscopic ovarian electrocautery in polycystic ovary syndrome resistant to clomiphene citrate: A comparative study. Tehran Uni Med J 2010;67:712-7.
[12] Kaya H, Sezik M, Ozkaya O. Evaluation of a new surgical approach for the treatment of clomiphene citrate-resistant infertility in polycystic ovary syndrome: Laparoscopic ovarian multi-needle intervention. J Minim Invasive Gynaecol. 2005;12:355-8.
[13] Lazovic G, Milacic D, Terzic M et al. Medicaments or surgical therapy of PCOS. Fertil Steril. 1998;70:472.
[14] Vegetti W, Ragni G, Baroni E et al. Laparoscopic ovarian drilling versus low-dose pure FSH in anovulatory clomiphene- resistant patients with polycystic ovarian syndrome: randomised prospective study. Hum Reprod. 1998;13:120.
[15] Casini ML, Rossi F, Agostini R et al. Effect of the position of fibroids on fertility Gynecol Endocrinol. 2006;22:106-9.
[16] Shokeir TA, Shalan HM, El-Shafei MM. Significance of endometrial polyps detected hysteroscopically in eumenorrheic infertile women. J Obstet Gynaecol Res. 2004;30:84-9
[17] Pérez-Medina T, Bajo-Arenas J, Salazar F et al. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective randomised study Hum Reprod. 2005;20:1632-5.
[18] Tanahatoe S, Lambalk CB, Hompes PGA. The role of lapa roscopy in intrauterine insemination: a prospective randomized reallocation study. Hum Reprod. 2005;20:3225-30.
[19] El-Toukhy T, Sunkara SK, Coomarasamy A et al. Outpatient hysteroscopy and subsequent IVF cycle outcome: a systematic review and meta-analysis RBM Online. 2008;16:712-9.
[20] Demirol A, Gurgan T. Effect of treatment of intrauterine pathologies with office hysteroscopy in patients with recurrent IVF failure Reprod Biomed Online. 2004;8:590-4.
[21] Gurgan T, Urman B, Aksu T et al. The effect of short-interval laparoscopic lysis of adhesions on pregnancy rates following Nd-YAG laser photocoagulation of polycystic ovaries. Obstet Gynecol. 1992;80:45-7.
[22] Muzii L, Bellati F, Bianchi A et al. Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part II: pathological results. Hum Reprod. 2005;20:1987-92.
[23] Exacoustos C, Zupi E, Amadio A et al. Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue. Am J Obstet Gynecol. 2004;191:68- 72.
[24] Gelbaya TA, Nardo LG, Fitzgerald CT et al. Ovarian response to gonadotropins after laparoscopic salpingectomy or the division of fallopian tubes for hydrosalpinges. Fertil Steril. 2006;85:1464-8.
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ABOUT THE AUTHOR
Kirsten Linnartz, MD
Kirsten Linnartz, MD is a recent graduate of Georgetown University School of Medicine in Washington, DC. She completed her undergraduate education at the United States Air Force Academy in Colorado Springs, CO followed by a masters at the University of Florida. She plans to pursue residency in obstetrics and gynecology and is interested in female infertility. She enrolled in the FACTS elective to gain more insight into natural family planning methods in order to share with her patients in the future.
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