Treatment of infertility associated with deep endometriosis Definition of therapeutic balances

Capsule:
We discuss how therapeutic decisions should be shared with women who have deep endometriosis after a comprehensive evaluation; an in depth and realistic review of the benefits and risks should be made clearly available.

Authors:
Edgardo Somigliana, M.D., Ph.D.,, Juan Antonio Garcia-Velasco, M.D., Ph.D.

Volume 104, Issue 4, Pages 764-770

Abstract:

Deep endometriosis is a demanding condition that is associated with infertility. However, evidence supporting a direct link between deep endometriosis and infertility is weak. In fact, infertility in affected patients is more likely to be explained by the strong association between deep endometriosis and adhesions, superficial endometriotic implants, ovarian endometriomas, and adenomyosis. The purported beneficial effects of surgery on infertility are mainly based on the 40%–42% pregnancy rate (PR) after surgery observed in published case series. However, this level of evidence is questionable and overestimates the benefits of the intervention. Even if comparative studies are lacking, IVF may be a valid alternative. The procedure may be less effective in affected women compared with other indications and it is not without additional deep endometriosis-related risks. Some case reports suggest that lesions might progress during IVF causing ureteral or intestinal complications or can decidualize during pregnancy causing intestinal perforation, pneumothorax, and pelvic vessels rupture. Finally, in the decision-making process, physicians should also consider that women with a history of deep endometriosis may face an increased risk of pregnancy complications. In conclusion, clear recommendation for the management of infertile women with deep endometriosis cannot be extrapolated from the literature. The therapeutic decision should be based on a comprehensive evaluation that includes clinical history, instrumental findings, pain symptoms, risks of pregnancy complications, and the woman’s wishes.

  • Dear Editor,

    We read with great interest the extremely good article of Somigliana
    and Garcia-Velasco (1) focusing on the relationship between infertility and deep
    endometriosis, and the therapeutic strategies that could be considered. They
    thoroughly discuss whether or not young patients with deep endometriosis actually
    need surgery, however less extensively their need of IVF to conceive.

    We agree that pregnancy rates (PR) in the series of patients managed by surgery cannot entirely be attributed to the surgical procedure, and several patients would have probably been pregnant even if the surgery had not been performed (1). Moreover, authors reporting the benefit of surgery on fertility should justify the existence of preoperative infertility, even though those patients were managed for stage 4 endometriosis, in which negative impact on spontaneous conception should no longer be demonstrated. Conversely, infertility in the series of patients managed
    by primary IVF does not need to be proven, because “case series of IVF are more
    informative than those of surgery », as « all observed pregnancies could
    be attributed to the procedure itself. »(1)

    In our opinion, the questions should be
    asked differently: What is the likelihood of pregnancy for a young patient with
    deep endometriosis and pregnancy desire by primary IVF or surgery? (2) Does a
    woman have more chances to be pregnant after a single or several IVF procedures
    than after surgery followed or not by IVF? (2,3) Does a patient take a higher
    risk by undergoing surgery or, conversely, in delaying the intervention for months
    or years? (2,4) Is it less expensive to manage patients by several primary IVF
    procedures or by a surgical intervention followed by spontaneous conception in
    up to two-thirds of cases? (4) Is surgery definitively avoided in patients
    undergoing primary IVF, or is it only postponed?

    If a comparative “intention to treat” randomized trial is performed in this topic in the future, it will specifically answer each of the questions listed above.

    In this way, it is interesting to review the comparative study of Bianchi et al (5)
    by obtaining the lacked data about patients who conceived spontaneously. Accordingly
    to the study’s design, women who spontaneously conceived were excluded from the
    study, as were those who declined postoperative IVF. Thus, the results of the
    study were reasonably different from those that would have been provided by an
    “intention to treat” study where all pregnancies should have been taken into
    account. To calculate the total PR, the number of patients who spontaneously
    conceived in each arm of the trial should be considered. Data was obtained upon
    request, and there were therefore 10 out of 115 patients with spontaneous
    conception in the primary IVF arm, giving a spontaneous PR of 8.7%. In the
    surgical arm, 18 out of 84 conceived spontaneously, resulting in a spontaneous
    PR 2.5 times higher (21.4%). Thus, the overall PR is 29.6% in the primary IVF
    arm vs. 51.2% in the surgical arm (P=0.003). By choosing surgery, patients from
    Sao Paolo increased their chances to conceive by 66% during the study follow
    up.

    Recent guidelines state that « The effectiveness of surgical excision of
    deep nodular lesions before treatment with assisted reproductive technologies
    in women with endometriosis-associated infertility is not well established in
    regard to reproductive outcomes (C) » (6). This means that surgery is not
    required once IVF decision has been made, if the sole goal of treatment is to
    increase PR following IVF. In daily practice, this statement is frequently
    misunderstood, leading to the systematic practice of primary IVF in women with
    deep endometriosis, because surgery is supposed to be of no effect in improving
    the PR. In numerous young patients, severe complaints occur rapidly after interrupting
    the contraceptive pill, and the diagnosis of deep endometriosis is affirmed.
    Consequently, they usually seek care after a couple of months of pregnancy
    attempts, and do not meet “infertility” criteria. When referred to medical
    teams who recommend primary IVF, they are automatically recorded as “infertile”
    and undergo IVF. On the other hand, when referred to teams where surgery is
    recommended to treat both pain and manage pregnancy intention, they undergo primary surgery with or without postoperative IVF (3). Ultimately, the major clinical
    outcome in all those young patients is the overall PR. To date, available data
    suggest that PR would be comparable and if not higher in patients referred to medical
    centers recommending surgery (2). In addition, in this latter case, deep endometriosis
    is treated. The rate of severe postoperative complications is low when patients
    are managed by experienced teams (in 405 patients managed for colorectal
    endometriosis from 2010 to 2015 in our center there were prospectively recorded:
    2.5% of rectovaginal fistulas, 0.25% leakages, 0.75% severe bladder dysfunction
    over 3 months postoperatively, and only 1 patient with Clavien 4 complication).
    Moreover, the rate of complications also concerns women who underwent primary
    IVF in whom surgery is merely postponed for years.

    As we recently exchanged at the last World Congress of Endometriosis in Sao Paolo, this exciting debate could only be closed by a large randomized trial in intention to treat
    comparing primary IVF to primary surgery in women with deep endometriosis and
    pregnancy wish (2).

    Horace Roman, MD PhD
    Basma Darwish, MD

    Department of Gynecology and
    Obstetrics
    Rouen University Hospital,
    France
    horace.roman@gmail.com

    References

    1. Somigliana
    E, Garcia-Velasco JA. Treatment of infertility associated with deep
    endometriosis: definition of therapeutic balances. Fertil Steril 2015; In press.
    DOI: http://dx.doi.org/10.1016/j.fertnstert.2015.08.003

    2. Roman H. Colorectal endometriosis and pregnancy wish: why doing primary

    surgery. Front Biosci (Schol Ed)
    2015;7:83–93.

    3. Roman H, Quibel S, Auber M, Muszynski H, Huet E, Marpeau L, Tuech
    JJ. Recurrences and fertility after
    endometrioma ablation in women with and without colorectal endometriosis: a
    prospective cohortstudy. Hum Reprod. 2015 Mar;30(3):558-68.

    4. Roman H, Puscasiu L, Lempicki M, Huet E, Chati R, Bridoux V, Tuech
    JJ, Abo C. Colorectal Endometriosis Responsible
    for Bowel Occlusion or Subocclusion in Women With Pregnancy Intention: Is
    the Policy of Primary in Vitro Fertilization Always Safe? J Minim Invasive Gynecol. 2015;22:1059-67.

    5. Bianchi PH, Pereira RM, Zanatta A, Alegretti JR, Motta EL,
    Serafini PC. Extensive excision of deep infiltrative endometriosis
    before in vitro fertilization significantly improves pregnancy rates. J Minim
    Invasive Gynecol 2009;16:174–80.

    6. Dunselman GAJ, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W. ESHRE guideline: management
    of women with endometriosis. Hum Reprod 2014 : 29: 400-12.

    • Juan Garcia-Velasco

      We fully agree with the comments from Dr Roman and Dr Darwish – there is today a lack of strong data to support clearly any direction. Thus, young asymptomatic women may choose surgery -considering the low incidence of complications in experienced hands, but sometimes severe, that may requiere additional surgery- whereas symptomatic women and “not-so-young” women will be directly managed with IVF as time is their most precious asset that cannot be wasted while waiting for a spontaneous pregnancy.

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