- Email: [email protected]
Differed surgery in patient with colorectal endometriosis and pregnancy intention: Is it reasonable?
Accepted Manuscript Title: Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable?Differed Surgery for Colorectal Endometriosis and pregnancy intention–> Author: Salma Touleimat Emmanuel Huet Sophie Sanguin Horace Roman PII: DOI: Reference:
S2468-7847(17)30221-0 https://doi.org/doi:10.1016/j.jogoh.2017.10.006 JOGOH 114
To appear in: Received date: Revised date: Accepted date:
13-3-2017 20-10-2017 25-10-2017
Please cite this article as: Salma TouleimatEmmanuel HuetSophie SanguinHorace Roman Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable?Differed Surgery for Colorectal Endometriosis and pregnancy intention–> (2017), https://doi.org/10.1016/j.jogoh.2017.10.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable? Short title : Differed Surgery for Colorectal Endometriosis and pregnancy intention.
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Salma Touleimat M.D.1, Emmanuel Huet M.D.2, Sophie Sanguin M.D.3, Horace Roman M.D., PhD1,4 1 Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France 2 Department of Digestive Surgery, Rouen University Hospital, Rouen, France 3 Department of Gynecology and Obstetrics, Amiens University Hospital, Amiens, France 4 Research Group 4308, Spermatogenesis and Gamete Quality, IHU Rouen Normandy, IFRMP23, Reproductive Biology Laboratory, Rouen University Hospital, Rouen, France
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Authors declare no conflict of interest
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Correspondence: Horace Roman, Department of Gynecology and Obstetrics, Rouen University Hospital-Charles Nicolle, 1 rue de Germont, 76031 Rouen, France, Tél: (33) 232 888 754; Fax: (33) 235 981 149; Email : [email protected]
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Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable? Abstract: The management of patients presenting deep infiltrating endometriosis involving the rectum (DIER) and pregnancy intention is controversial. Assisted Reproduction Techniques (ART) are often proposed first, but this may lead to complications and further difficulties managing DIER. A 29-years-old woman was diagnosed with pre-occlusive DIER. However, she was offered in-vitro fertilization (IVF) and underwent six unsuccessful cycles with serious complications: an ectopic pregnancy and a hemoperitoneum following arterial injury during oocyte retrieval, requiring two laparotomies in emergency. The patient’s symptoms worsened over time and colorectal resection with diverting colostomy was performed. The patient’s quality of life was then improved. In our opinion, prior ART in patients presenting DIER
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delays surgery and may have harmful complications. Therefore, primary surgery followed by ART may be a valuable option in some cases and should be discussed with the patients.
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Keywords : Colorectal endometriosis, pregnancy intention, Assisted reproduction, complications, differed surgery
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Introduction: One of the most exciting debates in endometriosis field concerns the management of patients presenting with deep infiltrating endometriosis of the rectum (DIER) and pregnancy intention. DIER is a severe type of endometriosis often associated with various pelvic localizations of the disease (ovaries, fallopian tubes, Douglas pouch) that negatively impact fertility. As a majority of patients with colorectal DIE are classified in the 4th stage of the disease according to the revised American Fertility Society (rAFS) classification (1), they are supposed infertile. For these reasons and with the aim of assuring the best pregnancy rate (PR), ART is most often offered before colorectal DIE surgery to shorten delay of conception and avoid risk of postoperative ovarian reserve impairment and the negative impact of potential postoperative complications on patient fertility (2,3). This attitude remains controversial for several reasons: i) the positive effect of surgery on overall PR (4,5), ii) the risk of disease progression with the multiple IVF cycles and the absence of amenorrhea in between (1), and iii) the risk of incidents following IVF puncture in women with frozen pelvis (6). We present the case of a young nullipara, which in itself illustrates the latter two issues mentioned above.
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Case Report: A 29-years-old woman presented a pregnancy intention since age 24, along with a polycystic ovary syndrome (PCOS). She underwent several cycles of Clomiphene Citrate treatment, with a spontaneous pregnancy occurring between two of those cycles and leading to spontaneous abortion at 7 weeks of gestation. DIE was diagnosed in 2010 with a history of dysmenorrhea starting in adolescence, dyspareunia, catamenial diarrhea and severely painful defecation during the menstrual cycles. There was no family history of endometriosis. While no preoperative imaging was performed, the patient had an explorative laparoscopy finding deep endometriosis with a frozen pelvis. Providing that the patient had a pregnancy intention, she was rather advised to undergo an in vitro fertilization (IVF) treatment. She underwent 6 cycles of IVF, of which the fifth was complicated by an ectopic pregnancy necessitating a prompt surgical management by median laparotomy with right salpingectomy. Then, the patient underwent a second median laparotomy for right ovarian artery lesion resulting from the 6th oocyte puncture. This latter laparotomy was complicated by a deep venous thrombosis revealing double mutation of Methylenetetrahydrofolate reductase (MTHFR). The IVF treatment was definitively stopped. The pelvic pain presented by the patient, as well as the cyclic symptoms, became worse over the years: catamenial dyschesia alternating with frequent liquid stools. The clinical
2
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examination showed a painful uterine mobilisation and no vaginal infiltration, suggesting that the deep endometriosis lesions might by highly situated. The Magnetic Reasonance Imaging (MRI) showed extensive endometriosis lesions affecting both of the utero-sacral ligaments, the torus and the upper rectum. The computed tomography-based virtual colonoscopy revealed that the rectal nodule measured 3 cm length, 15 mm thick and was at a distance of 14 cm from the anus. It reduced significantly the rectal diameter down to 5 mm (Fig 1). Endorectal ultrasound showed that the endometriosic lesion infiltrated the rectal wall deep into the submucosa. The surgery was performed laparoscopically and included extensive adhesiolysis, large colorectal resection with direct anastomosis, excision of uterine torus and posterior vagina, and diverting colostomy for three months. There was no post-operative complication. Short term follow-up found a remarkable improvement of the patient’s quality of life. Ovarian reserve did not postoperatively decrease. Spontaneous conception has been unsuccessfully attempted for 9 months, and then oocyte donation was proposed on the basis of clinical history. Discussion: The case illustrated the complications resulting from the policy of primary IVF in women with severe DIER and pregnancy intention. The patient underwent 6 cycles of IVF treatment with only an ectopic pregnancy, which management in emergency by open surgery was most challenging due to the presence of frozen pelvis. Furthermore, oocyte retrieval in frozen pelvis led to severe hemoperitoneum, resulting in second open surgery in emergency. Surgical management of DIE being delayed for 4 years, and it is most likely that the severity of the disease could progress from the 22 to the age 26. Even though no successive imaging assessments were performed to demonstrate the progression of colorectal involvement during this period of time, it is likely that this severe form of endometriosis was a progressive disease resulting from a rapid evolution from the age of first periods to that of 26. As “nobody is born with a stage 4 endometriosis” (regarde reference dans l’article Roman Gromez, Fertil Steril 2008), it is obvious that the progression of this disease occurred during only 12 years, among which during the latter 4 the patients was managed in ART with significant clinical progression. In our opinion, as most journals do not longer publish case reports, such events are not as unusual as one may believe, but rather underreported in the literature. There is a lack of high level of evidence trials in this field. Recent guidelines (3) state that surgery for DIE performed before IVF does not increase PR but that surgery may be required in patients with pelvic pain. However, the guidelines do not state neither that all the patients with DIE and pregnancy intention would require IVF, nor that these women would be still infertile after first line surgery. Several studies showed that surgery in advanced DIE may increase postoperative spontaneous PR by 25 to 37% (4,7,8). The risk of endometriosis related complications, such as bowel occlusion, rectal infiltration and ureteral stenosis, is logically reduced when surgery is performed earlier (1,9). It is also to be noted that conservative colorectal surgery by shaving or disc excision has probably a greater feasibility when performed early than when it is attempted in advanced stages of the disease, which lead to larger infiltrations of the digestive tract. The risk of postoperative complications such as bladder dysfunction or rectovaginal fistula is probably lower when surgery is performed in less advanced stages. On the other hand, these postoperative complications may negatively impact spontaneous conception and usually delay the implementation of postoperative IVF. The risk of significant reduction in ovarian reserve, leading to decrease of ovarian responsiveness during IVF hyprestimulation, is rather related to ovarian endometriomas cystectomy than to colorectal surgery itself (5) Worldwide meetings on endometriosis thrive on debates around the theme of the opinion here presented, with conclusions varying significantly from one conference to another according to speaker experience and views. An absence of consensus and inevitable divergent
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advice leave patients routinely confused with hesitation further delaying accurate management of the disease. Data available in the literature suggest that the current policy of systematic IVF prior to surgery in patients with colorectal DIE is, at least, questionable (4). When postoperative PR is taken into account along with expected disease development, primary surgery followed by spontaneous conception or ART may, in thouroughly selected cases, appear more suitable than primary ART. A definitive answer can be provided by a randomized trial, although sample size, length of follow up and cost may challenge feasibility.
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References: 1. Roman H, Puscasiu L, Lempicki M, Huet E, Chati R, Bridoux V, et al. 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 Oct;22(6):1059–67. 2. Ballester M, d’ Argent EM, Morcel K, Belaisch-Allart J, Nisolle M, Darai E. Cumulative pregnancy rate after ICSI-IVF in patients with colorectal endometriosis: results of a multicentre study. Hum Reprod. 2012 Apr 1;27(4):1043–9. 3. Dunselman GAJ, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar 1;29(3):400–12. 4. Roman H. Colorectal endometriosis and pregnancy wish: why doing primary surgery. Front Biosci Sch Ed. 2015;7:83–93. 5. Bianchi PHM, Pereira RMA, Zanatta A, Alegretti JR, Motta ELA, Serafini PC. Extensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates. J Minim Invasive Gynecol. 2009 Mar;16(2):174–80. 6. Bennett SJ, Waterstone JJ, Cheng WC, Parsons J. Complications of transvaginal ultrasound-directed follicle aspiration: a review of 2670 consecutive procedures. J Assist Reprod Genet. 1993 Jan;10(1):72–7. 7. Berlanda N, Vercellini P, Somigliana E, Frattaruolo M, Buggio L, Gattei U. Role of Surgery in Endometriosis-Associated Subfertility. Semin Reprod Med. 2013 Feb 27;31(02):133–43. 8. Daraï E, Cohen J, Ballester M. Colorectal endometriosis and fertility. Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:86–94. 9. Setúbal A, Sidiropoulou Z, Torgal M, Casal E, Lourenço C, Koninckx P. Bowel complications of deep endometriosis during pregnancy or in vitro fertilization. Fertil Steril. 2014 Feb;101(2):442–6.
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Figure Legends: Fig 1. Preoperative MRI and computed tomography based virtual colonoscopy revealing severe stenosis of digestive tract due to infiltration of upper rectum by deep endometriosis.
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S2468-7847(17)30221-0 https://doi.org/doi:10.1016/j.jogoh.2017.10.006 JOGOH 114
To appear in: Received date: Revised date: Accepted date:
13-3-2017 20-10-2017 25-10-2017
Please cite this article as: Salma TouleimatEmmanuel HuetSophie SanguinHorace Roman Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable?Differed Surgery for Colorectal Endometriosis and pregnancy intention–> (2017), https://doi.org/10.1016/j.jogoh.2017.10.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable? Short title : Differed Surgery for Colorectal Endometriosis and pregnancy intention.
us
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ip t
Salma Touleimat M.D.1, Emmanuel Huet M.D.2, Sophie Sanguin M.D.3, Horace Roman M.D., PhD1,4 1 Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France 2 Department of Digestive Surgery, Rouen University Hospital, Rouen, France 3 Department of Gynecology and Obstetrics, Amiens University Hospital, Amiens, France 4 Research Group 4308, Spermatogenesis and Gamete Quality, IHU Rouen Normandy, IFRMP23, Reproductive Biology Laboratory, Rouen University Hospital, Rouen, France
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Authors declare no conflict of interest
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an
Correspondence: Horace Roman, Department of Gynecology and Obstetrics, Rouen University Hospital-Charles Nicolle, 1 rue de Germont, 76031 Rouen, France, Tél: (33) 232 888 754; Fax: (33) 235 981 149; Email : [email protected]
Ac ce pt e
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49
Differed Surgery in Patient with Colorectal Endometriosis and pregnancy intention: Is it reasonable? Abstract: The management of patients presenting deep infiltrating endometriosis involving the rectum (DIER) and pregnancy intention is controversial. Assisted Reproduction Techniques (ART) are often proposed first, but this may lead to complications and further difficulties managing DIER. A 29-years-old woman was diagnosed with pre-occlusive DIER. However, she was offered in-vitro fertilization (IVF) and underwent six unsuccessful cycles with serious complications: an ectopic pregnancy and a hemoperitoneum following arterial injury during oocyte retrieval, requiring two laparotomies in emergency. The patient’s symptoms worsened over time and colorectal resection with diverting colostomy was performed. The patient’s quality of life was then improved. In our opinion, prior ART in patients presenting DIER
1
Page 1 of 5
delays surgery and may have harmful complications. Therefore, primary surgery followed by ART may be a valuable option in some cases and should be discussed with the patients.
cr
ip t
Keywords : Colorectal endometriosis, pregnancy intention, Assisted reproduction, complications, differed surgery
d
M
an
us
Introduction: One of the most exciting debates in endometriosis field concerns the management of patients presenting with deep infiltrating endometriosis of the rectum (DIER) and pregnancy intention. DIER is a severe type of endometriosis often associated with various pelvic localizations of the disease (ovaries, fallopian tubes, Douglas pouch) that negatively impact fertility. As a majority of patients with colorectal DIE are classified in the 4th stage of the disease according to the revised American Fertility Society (rAFS) classification (1), they are supposed infertile. For these reasons and with the aim of assuring the best pregnancy rate (PR), ART is most often offered before colorectal DIE surgery to shorten delay of conception and avoid risk of postoperative ovarian reserve impairment and the negative impact of potential postoperative complications on patient fertility (2,3). This attitude remains controversial for several reasons: i) the positive effect of surgery on overall PR (4,5), ii) the risk of disease progression with the multiple IVF cycles and the absence of amenorrhea in between (1), and iii) the risk of incidents following IVF puncture in women with frozen pelvis (6). We present the case of a young nullipara, which in itself illustrates the latter two issues mentioned above.
Ac ce pt e
50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99
Case Report: A 29-years-old woman presented a pregnancy intention since age 24, along with a polycystic ovary syndrome (PCOS). She underwent several cycles of Clomiphene Citrate treatment, with a spontaneous pregnancy occurring between two of those cycles and leading to spontaneous abortion at 7 weeks of gestation. DIE was diagnosed in 2010 with a history of dysmenorrhea starting in adolescence, dyspareunia, catamenial diarrhea and severely painful defecation during the menstrual cycles. There was no family history of endometriosis. While no preoperative imaging was performed, the patient had an explorative laparoscopy finding deep endometriosis with a frozen pelvis. Providing that the patient had a pregnancy intention, she was rather advised to undergo an in vitro fertilization (IVF) treatment. She underwent 6 cycles of IVF, of which the fifth was complicated by an ectopic pregnancy necessitating a prompt surgical management by median laparotomy with right salpingectomy. Then, the patient underwent a second median laparotomy for right ovarian artery lesion resulting from the 6th oocyte puncture. This latter laparotomy was complicated by a deep venous thrombosis revealing double mutation of Methylenetetrahydrofolate reductase (MTHFR). The IVF treatment was definitively stopped. The pelvic pain presented by the patient, as well as the cyclic symptoms, became worse over the years: catamenial dyschesia alternating with frequent liquid stools. The clinical
2
Page 2 of 5
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M
an
us
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ip t
examination showed a painful uterine mobilisation and no vaginal infiltration, suggesting that the deep endometriosis lesions might by highly situated. The Magnetic Reasonance Imaging (MRI) showed extensive endometriosis lesions affecting both of the utero-sacral ligaments, the torus and the upper rectum. The computed tomography-based virtual colonoscopy revealed that the rectal nodule measured 3 cm length, 15 mm thick and was at a distance of 14 cm from the anus. It reduced significantly the rectal diameter down to 5 mm (Fig 1). Endorectal ultrasound showed that the endometriosic lesion infiltrated the rectal wall deep into the submucosa. The surgery was performed laparoscopically and included extensive adhesiolysis, large colorectal resection with direct anastomosis, excision of uterine torus and posterior vagina, and diverting colostomy for three months. There was no post-operative complication. Short term follow-up found a remarkable improvement of the patient’s quality of life. Ovarian reserve did not postoperatively decrease. Spontaneous conception has been unsuccessfully attempted for 9 months, and then oocyte donation was proposed on the basis of clinical history. Discussion: The case illustrated the complications resulting from the policy of primary IVF in women with severe DIER and pregnancy intention. The patient underwent 6 cycles of IVF treatment with only an ectopic pregnancy, which management in emergency by open surgery was most challenging due to the presence of frozen pelvis. Furthermore, oocyte retrieval in frozen pelvis led to severe hemoperitoneum, resulting in second open surgery in emergency. Surgical management of DIE being delayed for 4 years, and it is most likely that the severity of the disease could progress from the 22 to the age 26. Even though no successive imaging assessments were performed to demonstrate the progression of colorectal involvement during this period of time, it is likely that this severe form of endometriosis was a progressive disease resulting from a rapid evolution from the age of first periods to that of 26. As “nobody is born with a stage 4 endometriosis” (regarde reference dans l’article Roman Gromez, Fertil Steril 2008), it is obvious that the progression of this disease occurred during only 12 years, among which during the latter 4 the patients was managed in ART with significant clinical progression. In our opinion, as most journals do not longer publish case reports, such events are not as unusual as one may believe, but rather underreported in the literature. There is a lack of high level of evidence trials in this field. Recent guidelines (3) state that surgery for DIE performed before IVF does not increase PR but that surgery may be required in patients with pelvic pain. However, the guidelines do not state neither that all the patients with DIE and pregnancy intention would require IVF, nor that these women would be still infertile after first line surgery. Several studies showed that surgery in advanced DIE may increase postoperative spontaneous PR by 25 to 37% (4,7,8). The risk of endometriosis related complications, such as bowel occlusion, rectal infiltration and ureteral stenosis, is logically reduced when surgery is performed earlier (1,9). It is also to be noted that conservative colorectal surgery by shaving or disc excision has probably a greater feasibility when performed early than when it is attempted in advanced stages of the disease, which lead to larger infiltrations of the digestive tract. The risk of postoperative complications such as bladder dysfunction or rectovaginal fistula is probably lower when surgery is performed in less advanced stages. On the other hand, these postoperative complications may negatively impact spontaneous conception and usually delay the implementation of postoperative IVF. The risk of significant reduction in ovarian reserve, leading to decrease of ovarian responsiveness during IVF hyprestimulation, is rather related to ovarian endometriomas cystectomy than to colorectal surgery itself (5) Worldwide meetings on endometriosis thrive on debates around the theme of the opinion here presented, with conclusions varying significantly from one conference to another according to speaker experience and views. An absence of consensus and inevitable divergent
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advice leave patients routinely confused with hesitation further delaying accurate management of the disease. Data available in the literature suggest that the current policy of systematic IVF prior to surgery in patients with colorectal DIE is, at least, questionable (4). When postoperative PR is taken into account along with expected disease development, primary surgery followed by spontaneous conception or ART may, in thouroughly selected cases, appear more suitable than primary ART. A definitive answer can be provided by a randomized trial, although sample size, length of follow up and cost may challenge feasibility.
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References: 1. Roman H, Puscasiu L, Lempicki M, Huet E, Chati R, Bridoux V, et al. 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 Oct;22(6):1059–67. 2. Ballester M, d’ Argent EM, Morcel K, Belaisch-Allart J, Nisolle M, Darai E. Cumulative pregnancy rate after ICSI-IVF in patients with colorectal endometriosis: results of a multicentre study. Hum Reprod. 2012 Apr 1;27(4):1043–9. 3. Dunselman GAJ, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar 1;29(3):400–12. 4. Roman H. Colorectal endometriosis and pregnancy wish: why doing primary surgery. Front Biosci Sch Ed. 2015;7:83–93. 5. Bianchi PHM, Pereira RMA, Zanatta A, Alegretti JR, Motta ELA, Serafini PC. Extensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates. J Minim Invasive Gynecol. 2009 Mar;16(2):174–80. 6. Bennett SJ, Waterstone JJ, Cheng WC, Parsons J. Complications of transvaginal ultrasound-directed follicle aspiration: a review of 2670 consecutive procedures. J Assist Reprod Genet. 1993 Jan;10(1):72–7. 7. Berlanda N, Vercellini P, Somigliana E, Frattaruolo M, Buggio L, Gattei U. Role of Surgery in Endometriosis-Associated Subfertility. Semin Reprod Med. 2013 Feb 27;31(02):133–43. 8. Daraï E, Cohen J, Ballester M. Colorectal endometriosis and fertility. Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:86–94. 9. Setúbal A, Sidiropoulou Z, Torgal M, Casal E, Lourenço C, Koninckx P. Bowel complications of deep endometriosis during pregnancy or in vitro fertilization. Fertil Steril. 2014 Feb;101(2):442–6.
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Figure Legends: Fig 1. Preoperative MRI and computed tomography based virtual colonoscopy revealing severe stenosis of digestive tract due to infiltration of upper rectum by deep endometriosis.
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