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Time to conceive after myomectomy: should we advise a minimum time interval? A systematic review

      Highlights

      • There is no proof of an ideal time interval after myomectomy to avoid uterine rupture.
      • Mean time from myomectomy to pregnancy is about 18 months.
      • Risk of uterine rupture is minimal after myomectomy.
      • Uterine rupture after myomectomy mainly occurs in the third trimester without labour.

      Abstract

      The optimal time interval between myomectomy and pregnancy is unclear and no specific guidelines exist. The aim of this review was to study the time interval from myomectomy to pregnancy and the occurrence of uterine rupture after myomectomy. Randomized controlled trials, cohort studies and retrospective studies were used to assess the primary objective, and case reports, cases series or letters to the editor for the secondary objective. Only articles reporting myomectomy performed via the vaginal route, laparotomy, laparoscopy or robot-assisted surgery were selected for inclusion. Among 3852 women who wanted to become pregnant after the surgery, 2889 became pregnant, accounting for 3000 pregnancies (77.9%) and 2097 live births (54.4%). Mean time between myomectomy and pregnancy was estimated at 17.6 months (SD 9.2) for 2451 pregnant women. Among 1016 women, a third were advised to delay attempting to conceive for between 3 and 6 months and another third for between 6 and 12 months. A total of 70 spontaneous uterine ruptures with a mean gestational age of 31 weeks at occurrence were identified. No linear relationship was found between gestational age at the event and time interval from myomectomy to conception (P = 0.706). There are insufficient data to advise a minimal time interval between myomectomy and conception.

      Keywords

      Introduction

      Uterine fibroids are common pelvic tumours occurring in almost 25% of women of childbearing age with symptoms due to myomas (
      • Buttram V.C.
      • Reiter R.C.
      Uterine leiomyomata: etiology, symptomatology, and management.
      ). The latter are responsible for many disorders: heavy and irregular bleeding, chronic or acute pelvic pain, and urinary and bowel discomfort. Other reproductive outcomes also appear to be due to myomas, such as infertility, miscarriage, abnormal placentation, preterm labour, labour dystocia and post-partum haemorrhage (
      • Shavell V.I.
      • Thakur M.
      • Sawant A.
      • Kruger M.L.
      • Jones T.B.
      • Singh M.
      • Puscheck E.E.
      • Diamond M.P.
      Adverse obstetric outcomes associated with sonographically identified large uterine fibroids.
      ; ;
      • Stewart E.A.
      • Cookson C.L.
      • Gandolfo R.A.
      • Schulze-Rath R.
      Epidemiology of uterine fibroids: a systematic review.
      ).
      Treatment of uterine fibroids is most often carried out when they become symptomatic or in case of infertility related to fibroids. Any treatment for myomas (medical treatment, myomectomy, embolization, high-intensity focused ultrasound) needs to be individualized and tailored to a woman's age, size and expectations about pregnancy (
      • Carranza-Mamane B.
      • Havelock J.
      • Hemmings R.
      on behalf of the Reproductive Endocrinology and Infertility Committee
      The management of uterine fibroids in women with otherwise unexplained infertility.
      ). Myomectomy is a surgical technique indicated for the removal of uterine myomas when a woman wishes to become pregnant later.
      The association between infertility and uterine myoma beyond stage II according to the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) classification (
      • Munro M.G.
      • Critchley H.O.D.
      • Broder M.S.
      • Fraser I.S.
      FIGO Working Group on Menstrual Disorders
      FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age.
      ) is still being debated: for intramural myomas, many studies have shown a trend towards pregnancy improvement after surgery when infertility arises (
      • Cook H.
      • Ezzati M.
      • Segars J.H.
      • McCarthy K.
      The impact of uterine leiomyomas on reproductive outcomes.
      ); for subserosal myomas, the benefits remain unclear (
      • Marret H.
      • Fritel X.
      • Ouldamer L.
      • Bendifallah S.
      • Brun J.-L.
      • De Jesus I.
      • Derrien J.
      • Giraudet G.
      • Kahn V.
      • Koskas M.
      • Legendre G.
      • Lucot J.P.
      • Niro J.
      • Panel P.
      • Pelage J.-P.
      • Fernandez H.
      CNGOF (French College of Gynecology and Obstetrics)
      Therapeutic management of uterine fibroid tumors: updated French guidelines.
      ). However, recent guidelines (American College of Obstetricians and Gynecologists [ACOG], American Society for Reproductive Medicine [ASRM], Collège National des Gynécologues et Obstétriciens Français [CNGOF]) have approved myomectomy for fertility improvement when fibroids are distorting the uterine cavity, or for symptomatic fibroids (
      American College of Obstetricians and Gynecologists
      ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas.
      ;
      • Marret H.
      • Fritel X.
      • Ouldamer L.
      • Bendifallah S.
      • Brun J.-L.
      • De Jesus I.
      • Derrien J.
      • Giraudet G.
      • Kahn V.
      • Koskas M.
      • Legendre G.
      • Lucot J.P.
      • Niro J.
      • Panel P.
      • Pelage J.-P.
      • Fernandez H.
      CNGOF (French College of Gynecology and Obstetrics)
      Therapeutic management of uterine fibroid tumors: updated French guidelines.
      ;
      Practice Committee of the American Society for Reproductive Medicine
      Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline.
      ).
      According to a recent meta-analysis, this surgery led to high pregnancy rates (75.6%) among 1575 women suffering from fibroids (
      • Khaw S.C.
      • Anderson R.A.
      • Lui M.-W.
      Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids.
      ). However, the operation can also be the source of severe obstetrical issues (abnormal placentation, uterine rupture, ectopic pregnancy on the myomectomy sites). Of these, uterine rupture is particularly feared because of its poor obstetric outcomes, even though it is rare (estimated between 0.1% and 1%) (
      • Gambacorti-Passerini Z.
      • Gimovsky A.C.
      • Locatelli A.
      • Berghella V.
      Trial of labor after myomectomy and uterine rupture: a systematic review.
      ;
      • Gil Y.
      • Badeghiesh A.
      • Suarthana E.
      • Mansour F.
      • Capmas P.
      • Volodarsky-Perel A.
      • Tulandi T.
      Risk of uterine rupture after myomectomy by laparoscopy or laparotomy.
      ).
      After a myomectomy, practitioners often advise a minimum delay before trying to conceive in order to avoid complications and to let the uterus heal. However, for infertile women, delaying the start of conception could be perceived or interpreted as a lost opportunity when ovarian function decreases with time (
      • Wilkosz P.
      • Greggains G.D.
      • Tanbo T.G.
      • Fedorcsak P.
      Female reproductive decline is determined by remaining ovarian reserve and age.
      ). Moreover, increasing the interval between surgery and conception may cause uterine fibroid recurrence, evaluated at between 34.2% and 41.6% at 3 years (
      • Kotani Y.
      • Tobiume T.
      • Fujishima R.
      • Shigeta M.
      • Takaya H.
      • Nakai H.
      • Suzuki A.
      • Tsuji I.
      • Mandai M.
      • Matsumura N.
      Recurrence of uterine myoma after myomectomy: open myomectomy versus laparoscopic myomectomy.
      ).
      Currently, there are no data about the ideal interval from myomectomy to pregnancy and the occurrence of spontaneous uterine rupture after myomectomy.
      As practices differ among physicians, the main objective of this review was to investigate the time interval from myomectomy to pregnancy across the literature. The secondary objective was to record this time interval through a comprehensive recording of cases of spontaneous uterine rupture during pregnancy after a previous myomectomy.

      Materials and methods

      Research methods

      This work was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement (
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ). The PubMed database was used for this search, initially using the keywords ‘myomectomy’ and ‘pregnancy’ and then the keywords ‘myomectomy’ and ‘uterine rupture’. Randomized controlled trials, cohort studies and retrospective studies were used to assess the primary objective, and case reports, cases series or letters to the editor for the secondary objective, dated from 2000 to September 2020. The references of all the publications identified were searched for other articles likely to provide reliable data for the purposes of this review.
      Selected articles had to be in English or French with the full-length article available. Only articles reporting myomectomy performed via the vaginal route (anterior and/or posterior colpotomy) (
      • Agostini A.
      • Deval B.
      • Birsan A.
      • Ronda I.
      • Bretelle F.
      • Roger V.
      • Cravello L.
      • Madelenat P.
      • Blanc B.
      Vaginal myomectomy using posterior colpotomy: feasibility in normal practice.
      ;
      • Davies A.
      • Hart R.
      • Magos A.L.
      The excision of uterine fibroids by vaginal myomectomy: a prospective study.
      ) or through laparotomy, laparoscopic or robotic assisted surgery were selected. It was decided to only include surgery that involved opening the uterus wall (laparoscopic, robotic, vaginal and abdominal myomectomy) and to only consider scarring of the uterus. In cases of hysteroscopic myomectomy, the myometrium is usually not opened and so it was decided to exclude hysteroscopic procedures.
      The protocol was registered through the PROSPERO database (no. CRD42020209898).

      Article selection process

      After a primary search, articles were selected in which the time between myomectomy and pregnancy was available as a mean or a median. For cases of uterine rupture, the interval between myomectomy and pregnancy had to be also mentioned. All types of uterine rupture or uterine dehiscence were considered, such as a thin uterine wall without myometrium and only the serous layer of the uterus. In these cases it was considered even if it was accidentally discovered during Caesarean section or during a routine ultrasound examination.
      The whole selection process was performed by three obstetrician and gynaecologist reviewers (TG, CA and FM) and was in accordance with the PRISMA statement.

      Data collection

      All data such as mean age, number of subjects treated, time from myomectomy to pregnancy, number of adverse events such as uterine rupture or ectopic pregnancy, time of delivery and mode of delivery were extracted independently by the three reviewers using a standardized data file. Data about previous myomectomy (number of myomas removed, age at pregnancy, time between pregnancy and myomectomy and date of the uterine rupture) were also gathered in order to obtain information about uterine rupture that was related to myomectomy.

      Statistical analysis

      For the main analysis, frequency weighting was used to assess different effects of each study according to the number of subjects. Linear regression was used to assess the correlation between time interval between myomectomy and pregnancy and gestational age at rupture.
      All analyses were performed using Stata Statistical Software, Release 15.1 (StataCorp LP, College Station, TX, USA).

      Results

      Review results

      Between January 2000 and the end of September 2020, 939 articles reporting on either myomectomy or pregnancy were identified through the PubMed database. Details of the article selection process are shown in Figure 1. Only 80 articles were considered eligible for this study, of which 43 articles met the primary objective of time interval between myomectomy and pregnancy. The 43 studies were from 15 different countries; 29 (67.4%) were retrospective studies (
      • Bernardi T.S.
      • Radosa M.P.
      • Weisheit A.
      • Diebolder H.
      • Schneider U.
      • Schleussner E.
      • Runnebaum I.B.
      Laparoscopic myomectomy: a 6-year follow-up single-center cohort analysis of fertility and obstetric outcome measures.
      ;
      • Borja de Mozota D.
      • Kadhel P.
      • Janky E.
      Fertility, pregnancy outcomes and deliveries following myomectomy: experience of a French Caribbean University Hospital.
      ;
      • Connolly G.
      • Doyle M.
      • Barrett T.
      • Byrne P.
      • De Mello M.
      • Harrison R.F.
      Fertility after abdominal myomectomy.
      ;
      • Dessolle L.
      • Soriano D.
      • Poncelet C.
      • Benifla J.-L.
      • Madelenat P.
      • Daraï E.
      Determinants of pregnancy rate and obstetric outcome after laparoscopic myomectomy for infertility.
      ;
      • Fauconnier A.
      • Dubuisson J.B.
      • Ancel P.Y.
      • Chapron C.
      Prognostic factors of reproductive outcome after myomectomy in infertile patients.
      ;
      • Fukuda M.
      • Tanaka T.
      • Kamada M.
      • Hayashi A.
      • Yamashita Y.
      • Terai Y.
      • Ohmichi M.
      Comparison of the perinatal outcomes after laparoscopic myomectomy versus abdominal myomectomy.
      ;
      • Huberlant S.
      • Lenot J.
      • Neron M.
      • Ranisavljevic N.
      • Letouzey V.
      • De Tayrac R.
      • Masia F.
      • Warembourg S.
      Fertility and obstetrical outcomes after robot-assisted laparoscopic myomectomy.
      ;
      • Kang M.
      • Kim J.
      • Kim T.-J.
      • Lee J.-W.
      • Kim B.-G.
      • Bae D.-S.
      • Choi C.H.
      Long-term outcomes of single-port laparoscopic myomectomy using a modified suture technique.
      ;
      • Kelly B.A.
      • Bright P.
      • Mackenzie I.Z.
      Does the surgical approach used for myomectomy influence the morbidity in subsequent pregnancy?.
      ;
      • Koo Y.-J.
      • Lee J.-K.
      • Lee Y.-K.
      • Kwak D.-W.
      • Lee I.-H.
      • Lim K.-T.
      • Lee K.-H.
      • Kim T.-J.
      Pregnancy outcomes and risk factors for uterine rupture after laparoscopic myomectomy: a single-center experience and literature review.
      ;
      • Kumakiri J.
      • Takeuchi H.
      • Kitade M.
      • Kikuchi I.
      • Shimanuki H.
      • Itoh S.
      • Kinoshita K.
      Pregnancy and delivery after laparoscopic myomectomy.
      ,
      • Kumakiri J.
      • Takeuchi H.
      • Itoh S.
      • Kitade M.
      • Kikuchi I.
      • Shimanuki H.
      • Kumakiri Y.
      • Kuroda K.
      • Takeda S.
      Prospective evaluation for the feasibility and safety of vaginal birth after laparoscopic myomectomy.
      ;
      • Lebovitz O.
      • Orvieto R.
      • James K.E.
      • Styer A.K.
      • Brown D.N.
      Predictors of reproductive outcomes following myomectomy for intramural fibroids.
      ;
      • Malzoni M.
      • Tinelli R.
      • Cosentino F.
      • Iuzzolino D.
      • Surico D.
      • Reich H.
      Laparoscopy versus minilaparotomy in women with symptomatic uterine myomas: short-term and fertility results.
      ;
      • Morita M.
      • Asakawa Y.
      Reproductive outcome after laparoscopic myomectomy for intramural myomas in infertile women with or without associated infertility factors: laparoscopic myomectomy for myomas.
      ;
      • Paul P.G.
      • Koshy A.K.
      • Thomas T.
      Pregnancy outcomes following laparoscopic myomectomy and single-layer myometrial closure.
      ;
      • Pepin K.
      • Dmello M.
      • Sandberg E.
      • Hill-Verrochi C.
      • Maghsoudlou P.
      • Ajao M.
      • Cohen S.L.
      • Einarsson J.I.
      Reproductive outcomes following use of barbed suture during laparoscopic myomectomy.
      ;
      • Pitter M.C.
      • Srouji S.S.
      • Gargiulo A.R.
      • Kardos L.
      • Seshadri-Kreaden U.
      • Hubert H.B.
      • Weitzman G.A.
      Fertility and symptom relief following robot-assisted laparoscopic myomectomy.
      ,
      • Pitter M.C.
      • Gargiulo A.R.
      • Bonaventura L.M.
      • Lehman J.S.
      • Srouji S.S.
      Pregnancy outcomes following robot-assisted myomectomy.
      ;
      • Pundir J.
      • Kopeika J.
      • Harris L.
      • Krishnan N.
      • Uwins C.
      • Siozos A.
      • Khalaf Y.
      • El-Toukhy T.
      Reproductive outcome following abdominal myomectomy for a very large fibroid uterus.
      ;
      • Rovio P.H.
      • Heinonen P.K.
      Pregnancy outcomes after transvaginal myomectomy by colpotomy.
      ;
      • Seinera P.
      • Farina C.
      • Todros T.
      Laparoscopic myomectomy and subsequent pregnancy: results in 54 patients.
      ;
      • Seracchioli R.
      • Manuzzi L.
      • Vianello F.
      • Gualerzi B.
      • Savelli L.
      • Paradisi R.
      • Venturoli S.
      Obstetric and delivery outcome of pregnancies achieved after laparoscopic myomectomy.
      ;
      • Soriano D.
      • Dessolle L.
      • Poncelet C.
      • Benifla J.L.
      • Madelenat P.
      • Darai E.
      Pregnancy outcome after laparoscopic and laparoconverted myomectomy.
      ;
      • Tian Y.
      • Long T.
      • Dai Y.
      Pregnancy outcomes following different surgical approaches of myomectomy: pregnancy outcomes after TAM and LM.
      ;
      • Tsuji I.
      • Fujinami N.
      • Kotani Y.
      • Tobiume T.
      • Aoki M.
      • Murakami K.
      • Kanto A.
      • Takaya H.
      • Ukita M.
      • Shimaoka M.
      • Nakai H.
      • Suzuki A.
      • Mandai M.
      Reproductive outcome of infertile patients with fibroids based on the patient and fibroid characteristics; optimal and personalized management.
      ;
      • Tusheva O.A.
      • Gyang A.
      • Patel S.D.
      Reproductive outcomes following robotic-assisted laparoscopic myomectomy (RALM).
      ;
      • Yoshino O.
      • Nishii O.
      • Osuga Y.
      • Asada H.
      • Okuda S.
      • Orisaka M.
      • Hori M.
      • Fujiwara T.
      • Hayashi T.
      Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate.
      ;
      • Zhang Y.
      • Hua K.Q.
      Patients’ age, myoma size, myoma location, and interval between myomectomy and pregnancy may influence the pregnancy rate and live birth rate after myomectomy.
      ), nine (20.9%) were prospective or cohort studies (
      • Cela V.
      • Freschi L.
      • Simi G.
      • Tana R.
      • Russo N.
      • Artini P.G.
      • Pluchino N.
      Fertility and endocrine outcome after robot-assisted laparoscopic myomectomy (RALM).
      ;
      • Chang W.-C.
      • Chang D.-Y.
      • Huang S.-C.
      • Shih J.-C.
      • Hsu W.-C.
      • Chen S.-Y.
      • Sheu B.-C.
      Use of three-dimensional ultrasonography in the evaluation of uterine perfusion and healing after laparoscopic myomectomy.
      ;
      • Chen S.-Y.
      • Sheu B.-C.
      • Huang S.-C.
      • Chang W.-C.
      Laparoendoscopic single-site myomectomy using conventional laparoscopic instruments and glove port technique: Four years experience in 109 cases.
      ;
      • Lönnerfors C.
      • Persson J.
      Robot-assisted laparoscopic myomectomy; a feasible technique for removal of unfavorably localized myomas.
      ,
      • Lönnerfors C.
      • Persson J.
      Pregnancy following robot-assisted laparoscopic myomectomy in women with deep intramural myomas.
      ;
      • Nishida M.
      • Ichikawa R.
      • Arai Y.
      • Sakanaka M.
      • Otsubo Y.
      New myomectomy technique for diffuse uterine leiomyomatosis.
      ;
      • Plotti G.
      • Plotti F.
      • Di Giovanni A.
      • Battaglia F.
      • Nagar G.
      Feasibility and safety of vaginal myomectomy: a prospective pilot study.
      ;
      • Tinelli A.
      • Hurst B.S.
      • Mettler L.
      • Tsin D.A.
      • Pellegrino M.
      • Nicolardi G.
      • Dell'Edera D.
      • Malvasi A.
      Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study.
      ;
      • Wu G.
      • Li R.
      • He M.
      • Pu Y.
      • Wang J.
      • Chen J.
      • Qi H.
      A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.
      ), and five (11.6%) were prospective randomized studies (
      • Kameda S.
      • Toyoshima M.
      • Tanaka K.
      • Fujii O.
      • Iida S.-I.
      • Yaegashi N.
      • Murakami T.
      • Hoshi K.
      Utility of laparoscopic uterine myomectomy as a treatment for infertility with no obvious cause except for uterine fibroids.
      ;
      • Kim H.-S.
      • Oh S.-Y.
      • Choi S.-J.
      • Park H.-S.
      • Cho G.-J.
      • Chung J.-H.
      • Seo Y.-S.
      • Jung S.-Y.
      • Kim J.-E.
      • Chae S.-H.
      • Hwang H.-S.
      Uterine rupture in pregnancies following myomectomy: a multicenter case series.
      ;
      • Kubinova K.
      • Mara M.
      • Horak P.
      • Kuzel D.
      • Dohnalova A.
      Reproduction after myomectomy: comparison of patients with and without second-look laparoscopy.
      ;
      • Mara M.
      • Maskova J.
      • Fucikova Z.
      • Kuzel D.
      • Belsan T.
      • Sosna O.
      Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy.
      ;
      • Samejima T.
      • Koga K.
      • Nakae H.
      • Wada-Hiraike O.
      • Fujimoto A.
      • Fujii T.
      • Osuga Y.
      Identifying patients who can improve fertility with myomectomy.
      ). In addition, 37 articles presented summaries or case reports of uterine rupture during pregnancy after myomectomy (n = 37) (
      • Abbas A.M.
      • Michael A.
      • Ali S.S.
      • Makhlouf A.A.
      • Ali M.N.
      • Khalifa M.A.
      Spontaneous prelabour recurrent uterine rupture after laparoscopic myomectomy.
      ;
      • Asakura H.
      • Oda T.
      • Tsunoda Y.
      • Matsushima T.
      • Kaseki H.
      • Takeshita T.
      A case report: change in fetal heart rate pattern on spontaneous uterine rupture at 35 weeks gestation after laparoscopically assisted myomectomy.
      ;
      • Banas T.
      • Klimek M.
      • Fugiel A.
      • Skotniczny K.
      Spontaneous uterine rupture at 35 weeks’ gestation, 3 years after laparoscopic myomectomy, without signs of fetal distress.
      ;
      • Cho H.
      Rupture of a myomectomy site in the third trimester of pregnancy after myomectomy, septoplasty and cesarean section: a case report.
      ;
      • Foucher F.
      • Levêque J.
      • Le Bouar G.
      • Grall J.
      Uterine rupture during pregnancy following myomectomy via coelioscopy.
      ;
      • Fukutani R.
      • Hasegawa J.
      • Arakaki T.
      • Oba T.
      • Nakamura M.
      • Sekizawa A.
      Silent uterine rupture occluded by intestinal adhesions following laparoscopic myomectomy: a case report.
      ;
      • Goynumer G.
      • Teksen A.
      • Durukan B.
      • Wetherilt L.
      Spontaneous uterine rupture during a second trimester pregnancy with a history of laparoscopic myomectomy.
      ;
      • Grande N.
      • Catalano G.F.
      • Ferrari S.
      • Marana R.
      Spontaneous uterine rupture at 27 weeks of pregnancy after laparoscopic myomectomy.
      ;
      • Hagneré P.
      • Denoual I.
      • Souissi A.
      • Deswarte S.
      [Spontaneous uterine rupture after myomectomy. Case report and review of the literature].
      ;
      • Hasbargen U.
      • Summerer-Moustaki M.
      • Hillemanns P.
      • Scheidler J.
      • Kimmig R.
      • Hepp H.
      Uterine dehiscence in a nullipara, diagnosed by MRI, following use of unipolar electrocautery during laparoscopic myomectomy: case report.
      ;
      • Hawkins L.
      • Robertson D.
      • Frecker H.
      • Berger H.
      • Satkunaratnam A.
      Spontaneous uterine rupture and surgical repair at 21 weeks gestation with progression to live birth: a case report.
      ;
      • Hortu İ.
      • Akdemir A.
      • Şendağ F.
      • Öztekin M.K.
      Uterine rupture in pregnancy after robotic myomectomy.
      ;
      • Iemura A.
      • Kondoh E.
      • Kawasaki K.
      • Fujita K.
      • Ueda A.
      • Mogami H.
      • Baba T.
      • Konishi I.
      Expectant management of a herniated amniotic sac presenting as silent uterine rupture: a case report and literature review.
      ;
      • Jakiel G.
      • Sobstyl M.
      • Swatowski D.
      Spontaneous uterine rupture during delivery in a patient who had previously undergone laparoscopic myomectomy.
      ;
      • Kacperczyk J.
      • Bartnik P.
      • Romejko-Wolniewicz E.
      • Dobrowolska-Redo A.
      Postmyomectomic uterine rupture despite Cesarean section.
      ;
      • Kim H.-S.
      • Oh S.-Y.
      • Choi S.-J.
      • Park H.-S.
      • Cho G.-J.
      • Chung J.-H.
      • Seo Y.-S.
      • Jung S.-Y.
      • Kim J.-E.
      • Chae S.-H.
      • Hwang H.-S.
      Uterine rupture in pregnancies following myomectomy: a multicenter case series.
      ;
      • Kiseli M.
      • Artas H.
      • Armagan F.
      • Dogan Z.
      Spontaneous rupture of uterus in midtrimester pregnancy due to increased uterine pressure with previous laparoscopic myomectomy.
      ;
      • Kuwata T.
      • Matsubara S.
      • Usui R.
      • Uchida S.-I.
      • Sata N.
      • Suzuki M.
      Intestinal adhesion due to previous uterine surgery as a risk factor for delayed diagnosis of uterine rupture: a case report.
      ;
      • Lieng M.
      • Istre O.
      • Langebrekke A.
      Uterine rupture after laparoscopic myomectomy.
      ;
      • Mahajan N.
      • Moretti M.L.
      • Lakhi N.A.
      Spontaneous early first and second trimester uterine rupture following robotic-assisted myomectomy.
      ;
      • Matsunaga J.S.
      • Daly C.B.
      • Bochner C.J.
      • Agnew C.L.
      Repair of uterine dehiscence with continuation of pregnancy.
      ;
      • Nkemayim D.C.
      • Hammadeh M.E.
      • Hippach M.
      • Mink D.
      • Schmidt W.
      Uterine rupture in pregnancy subsequent to previous laparoscopic electromyolysis. Case report and review of the literature.
      ;
      • Okada Y.
      • Hasegawa J.
      • Mimura T.
      • Arakaki T.
      • Yoshikawa S.
      • Yamashita Y.
      • Oba T.
      • Nakamura M.
      • Matsuoka R.
      • Sekizawa A.
      Uterine rupture at 10 weeks of gestation after laparoscopic myomectomy.
      ;
      • Oktem O.
      • Gökaslan H.
      • Durmusoglu F.
      Spontaneous uterine rupture in pregnancy 8 years after laparoscopic myomectomy.
      ;
      • Pakniat H.
      • Soofizadeh N.
      • Khezri M.B.
      Spontaneous uterine rupture after abdominal myomectomy at the gestational age of 20 weeks in pregnancy: a case report.
      ;
      • Parker W.H.
      • Iacampo K.
      • Long T.
      Uterine rupture after laparoscopic removal of a pedunculated myoma.
      ;
      • Pistofidis G.
      • Makrakis E.
      • Balinakos P.
      • Dimitriou E.
      • Bardis N.
      • Anaf V.
      Report of 7 uterine rupture cases after laparoscopic myomectomy: update of the literature.
      ;
      • Skrablin S.
      • Banovic V.
      • Kuvacic I.
      Successful pregnancy after spontaneous rupture of scarred uterus following fundal myomectomy.
      ;
      • Song S.-Y.
      • Yoo H.-J.
      • Kang B.-H.
      • Ko Y.-B.
      • Lee K.-H.
      • Lee M.
      Two pregnancy cases of uterine scar dehiscence after laparoscopic myomectomy.
      ;
      • Sutton C.
      • Standen P.
      • Acton J.
      • Griffin C.
      Spontaneous uterine rupture in a preterm pregnancy following myomectomy. Case Rep.
      ;
      • Tauchi M.
      • Hasegawa J.
      • Oba T.
      • Arakaki T.
      • Takita H.
      • Nakamura M.
      • Sekizawa A.
      A case of uterine rupture diagnosed based on routine focused assessment with sonography for obstetrics.
      ;
      • Tomczyk K.M.
      • Wilczak M.
      • Rzymski P.
      Uterine rupture at 28 weeks of gestation after laparoscopic myomectomy – a case report.
      ;
      • Torbé A.
      • Mikołajek-Bedner W.
      • Kałużyński W.
      • Gutowska-Czajka D.
      • Kwiatkowski S.
      • Błogowski W.
      • Rzepka R.
      • Czajka R.
      Uterine rupture in the second trimester of pregnancy as an iatrogenic complication of laparoscopic myomectomy.
      ;
      • Vimercati A.
      • Del Vecchio V.
      • Chincoli A.
      • Malvasi A.
      • Cicinelli E.
      Uterine rupture after laparoscopic myomectomy in two cases: real complication or malpractice? Case Rep.
      ;
      • Wachira L.
      • De Silva L.
      • Orangun I.
      • Shehzad S.
      • Kulkarni A.
      • Yoong W.
      Spontaneous preterm recurrent fundal uterine rupture at 26 weeks following laparoscopic myomectomy.
      ;
      • Wu X.
      • Jiang W.
      • Xu H.
      • Ye X.
      • Xu C.
      Characteristics of uterine rupture after laparoscopic surgery of the uterus: clinical analysis of 10 cases and literature review.
      ;
      • Yazawa H.
      • Takiguchi K.
      • Ito F.
      • Fujimori K.
      Uterine rupture at 33rd week of gestation after laparoscopic myomectomy with signs of fetal distress. A case report and review of literature.
      ).
      Figure 1
      Figure 1Flow chart showing the article selection process.

      Time from myomectomy to conception

      Altogether, the selected articles represented 7335 myomectomies performed for various conditions: infertility, heavy menstrual bleeding, pelvic discomfort. According to the data provided within the articles, laparoscopy was reported in 65.1% of studies (n = 28), followed by laparotomy (37.2%, n = 16), then robotic surgery (18.6%, n = 8) and a few studies reported vaginal myomectomy (7.0%, n = 3) (some studies reported more than one technique). A total of 3852 patients declared a wish to become pregnant (immediately after the surgery or later), equating to 52.5% of the myomectomies performed. Of these, 2889 became pregnant, accounting for 3000 pregnancies and 2097 live births. The conception rate was evaluated at 77.9% when live birth rate was at 54.4%. General statistics are detailed in Table 1. Among women who became pregnant (n = 2889), 35.2% (1016 women) were advised to delay before conceiving after myomectomy. For those advised to delay for between 0 and 3 months, the interval time advised was at 2 months.
      Table 1Summary statistics of pregnant women (n = 2889) after myomectomy
      Characteristicn (%) or mean (SD)
      Age, years (n = 1840)32.9 (2.0)
      Size of largest myoma (mm) (n = 776)126.7 (43.7)
      Mean size of myoma (mm) (n = 1593)58.0 (9.4)
      Number of myomas removed (n = 1267)3.0 (1.2)
      Advice concerning time interval between myomectomy and attempting to conceive (n = 2889)
       Not mentioned1873 (64.8)
       Instruction with time interval878 (30.4)
       Medical contraception during specified time interval138 (4.8)
      Interval time instructions from myomectomy to attempting to conceive (months) (n = 1016)
       0<interval time<352 (5.1)
       3≤interval time<6345 (34.0)
       6≤interval time<12412 (40.6)
       Interval time ≥12207 (20.4)
      Time from myomectomy to first pregnancy (n = 2889) (months)
       Interval from myomectomy to pregnancy (n = 2451)17.6 (9.2)
       Shortest interval from myomectomy to pregnancy
      Reported in 34 studies.
      4.3 (3.9)
      Pregnancy outcomes (n = 3000)
       Live birth2097 (69.9)
       Miscarriages439 (14.6)
       Late miscarriages28 (0.9)
       Ectopic pregnancy42 (1.4)
       Missing data394 (13.1)
       Uterine rupture (n = 3000)15 (0.5)
      Mode of delivery (n = 2070)
       Caesarean section1362 (65.8)
       Vaginal delivery708 (34.2)
      a Reported in 34 studies.
      The mean time between myomectomy and pregnancy was estimated at 17.6 months (SD 9.2) for 2451 pregnant women (within 34 studies). For studies describing median time from myomectomy to pregnancy, it was estimated at 13.3 months (SD 4.2) based on 399 pregnancies (within nine studies). The distribution of these intervals based on the size of the study is detailed in Figure 2. For 34 studies, the shortest or minimal time from myomectomy to conception was reported as between 1 and 14 months (mean estimated at 4.3 months [SD 3.9]). Among nine studies the shortest time from myomectomy to pregnancy was reported at 1 month. Most deliveries were performed by Caesarean section (62.4% of the living deliveries, n = 2097). Only 15 cases of spontaneous uterine rupture occurred (0.5% of all pregnancy) in all studies.
      Figure 2
      Figure 2Distribution of mean time interval from myomectomy to pregnancy according to studies (n = 34).

      Occurrence of uterine rupture

      Details of 70 spontaneous uterine rupture cases were obtained from 40 articles (37 case reports or case series and eight others depicted in other studies previously described in the main analysis [
      • Koo Y.-J.
      • Lee J.-K.
      • Lee Y.-K.
      • Kwak D.-W.
      • Lee I.-H.
      • Lim K.-T.
      • Lee K.-H.
      • Kim T.-J.
      Pregnancy outcomes and risk factors for uterine rupture after laparoscopic myomectomy: a single-center experience and literature review.
      ;
      • Tian Y.
      • Long T.
      • Dai Y.
      Pregnancy outcomes following different surgical approaches of myomectomy: pregnancy outcomes after TAM and LM.
      ;
      • Wu G.
      • Li R.
      • He M.
      • Pu Y.
      • Wang J.
      • Chen J.
      • Qi H.
      A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.
      ]).
      The main characteristics of these cases are detailed in Table 2. Most of the ruptures were reported after laparoscopic myomectomy (75.7%) whereas a few were described after robotic surgery (2.9%). The mean time between myomectomy and conception was 26.1 months (SD 22.7 months) with a median time at 17.5 months. Furthermore, mean gestational age when the uterine rupture occurred was calculated at 31.0 weeks (SD 7.0 weeks), when median time was reported at 33 weeks. Among all these cases, five (7.1%) were twin pregnancies. Placenta accreta has been reported for only one case.
      Table 2Characteristics of 70 cases of uterine rupture after myomectomy
      Characteristicn (%) or mean (SD)
      Age (years)34.7 (4.0)
      Type of surgery
       Laparotomy15 (21.4)
       Laparoscopy53 (75.7)
       Robotic surgery2 (2.9)
      Number of myomas removed (n = 51)5.4 (16.4)
      Size of largest myoma (cm) (n = 44)5.8 (2.5)
      Uterine cavity entered
       No37 (52.9)
       Yes7 (10.0)
       Not detailed26 (37.1)
      Previous uterine surgery
      Myomectomy and/or previous Caesarean section.
       No38 (54.3)
       Yes8 (11.4)
       Not detailed24 (34.3)
      Time from myomectomy to conception (months)26.1 (22.7)
      Gestational age at uterine rupture (weeks)31.0 (7.0)
      Timing of uterine rupture
       During labour3 (4.3)
       Without labour67 (95.7)
      a Myomectomy and/or previous Caesarean section.
      Among the cases, seven women only had a myometrial defect, with the serosal layer covering the uterine scar remaining intact (
      • Iemura A.
      • Kondoh E.
      • Kawasaki K.
      • Fujita K.
      • Ueda A.
      • Mogami H.
      • Baba T.
      • Konishi I.
      Expectant management of a herniated amniotic sac presenting as silent uterine rupture: a case report and literature review.
      ;
      • Matsunaga J.S.
      • Daly C.B.
      • Bochner C.J.
      • Agnew C.L.
      Repair of uterine dehiscence with continuation of pregnancy.
      ;
      • Tian Y.
      • Long T.
      • Dai Y.
      Pregnancy outcomes following different surgical approaches of myomectomy: pregnancy outcomes after TAM and LM.
      ;
      • Wu G.
      • Li R.
      • He M.
      • Pu Y.
      • Wang J.
      • Chen J.
      • Qi H.
      A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.
      ). All were confirmed during surgery (Caesarean section or exploratory surgery) and successfully repaired. Of these, one case was reported of a uterine dehiscence repaired while the pregnancy was still ongoing, allowing a live birth 6 weeks after the surgery (
      • Matsunaga J.S.
      • Daly C.B.
      • Bochner C.J.
      • Agnew C.L.
      Repair of uterine dehiscence with continuation of pregnancy.
      ). A case report of a uterine rupture covered by intestinal adhesion has also been described (
      • Kuwata T.
      • Matsubara S.
      • Usui R.
      • Uchida S.-I.
      • Sata N.
      • Suzuki M.
      Intestinal adhesion due to previous uterine surgery as a risk factor for delayed diagnosis of uterine rupture: a case report.
      ).
      Figure 3 depicts the distribution between time from myomectomy to uterine rupture and time of pregnancy. Most of the ruptures (75.7%, n = 53) occurred in the third trimester of pregnancy (above 28 gestational weeks). No correlation was found with the interval between myomectomy and pregnancy and the time of occurrence of spontaneous uterine rupture during pregnancy (P = 0.706). A few cases of uterine rupture occurred during labour (4.3%), whereas most of them occurred without any onset of labour (95.7%).
      Figure 3
      Figure 3Distribution between gestational age at uterine rupture and time from myomectomy to pregnancy.

      Discussion

      This review was designed to investigate time between myomectomy and pregnancy and whether this interval might influence the occurrence of uterine rupture, which is the most serious complication after myomectomy when pregnancy is ongoing. Mean time between myomectomy and pregnancy appears to be at 17.6 months, which is almost a year and half, and median time was estimated at 13.3 months. Furthermore, the shortest time from myomectomy to pregnancy was calculated, with a mean at 4.3 months among 34 studies. Within the 43 reports that have been used in this study, 16 mentioned the recommendation of a time interval between myomectomy and pregnancy, representing 1016 women. Of these, women were advised to wait after the surgery as follows: 5.1% from 0 to 3 months, 34.0% from 3 to 6 months, 40.6% from 6 to 12 months, and 20.4% above 12 months. One study reported the use of medical contraception to respect this time interval.
      With 3000 pregnancies among 3852 women who wished to become pregnant, the pregnancy rate was estimated at 77.9% (3000/3852), with 75.0% (2889/3852) of women achieving pregnancy, and the live birth rate at 54.4% (2097/3852). Uterine rupture occurred only 15 times, a rate of occurrence of 0.5%. Despite a very heterogeneous collection of data, these results seem to be in accordance with a recent review by
      • Khaw S.C.
      • Anderson R.A.
      • Lui M.-W.
      Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids.
      who found, in a population of 1575 pregnancies, a live birth rate of 75.6% (whereas it was 66.9% in this study). Also, the rate of uterine rupture calculated at 0.5% in this study appears to be reliable because for
      • Gil Y.
      • Badeghiesh A.
      • Suarthana E.
      • Mansour F.
      • Capmas P.
      • Volodarsky-Perel A.
      • Tulandi T.
      Risk of uterine rupture after myomectomy by laparoscopy or laparotomy.
      it was 0.44% in a population of 54,146 myomectomies followed by pregnancy (237 uterine ruptures) and 0.6% for
      • Khaw S.C.
      • Anderson R.A.
      • Lui M.-W.
      Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids.
      (1575 pregnancies after myomectomy, 10 uterine ruptures). This rate seems close to that of uterine rupture occurring in pregnancies following Caesarean delivery, which was estimated at between 0.7% and 1.1% (
      • Landon M.B.
      • Hauth J.C.
      • Leveno K.J.
      • Spong C.Y.
      • Leindecker S.
      • Varner M.W.
      • Moawad A.H.
      • Caritis S.N.
      • Harper M.
      • Wapner R.J.
      • Sorokin Y.
      • Miodovnik M.
      • Carpenter M.
      • Peaceman A.M.
      • O'Sullivan M.J.
      • Sibai B.
      • Langer O.
      • Thorp J.M.
      • Ramin S.M.
      • Mercer B.M.
      • Gabbe S.G.
      National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
      Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery.
      ;
      • Thisted D.L.A.
      • Mortensen L.H.
      • Hvidman L.
      • Rasmussen S.C.
      • Larsen T.
      • Krebs L.
      Use of ICD-10 codes to monitor uterine rupture: validation of a national birth registry.
      ).
      Most uterine ruptures seemed to occur in the third trimester and there was no proven relationship between time from myomectomy to conception and gestational age of occurrence (P = 0.706). Besides, uterine ruptures were very heterogeneously distributed as regards the time lapse between myomectomy and conception, which ranged from 1.5 to 88 months. Out of 44 uterine ruptures with information concerning uterine wall interruption, only seven events occurred when the uterine cavity had been entered during the previous myomectomy. Abnormal placenta position did not appear to be associated with the risk of uterine rupture, as only one case of placenta accreta has been reported (
      • Koo Y.-J.
      • Lee J.-K.
      • Lee Y.-K.
      • Kwak D.-W.
      • Lee I.-H.
      • Lim K.-T.
      • Lee K.-H.
      • Kim T.-J.
      Pregnancy outcomes and risk factors for uterine rupture after laparoscopic myomectomy: a single-center experience and literature review.
      ). Moreover, most of the events occurred without a trial of labour, which indicates that uterine rupture after a myomectomy seems to be a non-predictable complication. These results are in accordance with
      • Dubuisson J.-B.
      Pregnancy outcome and deliveries following laparoscopic myomectomy.
      , who report only three cases of uterine rupture in a series of 100 women who had had a previous myomectomy and who delivered. Even if the time from surgery to pregnancy was not known, no cases of uterine rupture occurred during labour in this study. Women who undergo myomectomy should be aware that this situation could happen at any time during the pregnancy, especially during the third trimester. They need to be informed about the clinical signs (acute abdominal pain, bleeding) that may suggest the occurrence of this threatening condition.
      Uterus healing after a myomectomy is a process that may involve many factors (use of coagulation, surgical technique, implications of growth factors, myogenesis versus fibrosis). It is known that ultrasound has proved that the scar area improves with time after myomectomy (
      • Tinelli A.
      • Hurst B.S.
      • Mettler L.
      • Tsin D.A.
      • Pellegrino M.
      • Nicolardi G.
      • Dell'Edera D.
      • Malvasi A.
      Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study.
      ). Evaluation after abdominal versus laparoscopic myomectomy does not seem to demonstrate any difference in healing when evaluating the uterine scar with ultrasound (
      • Asgari Z.
      • Salehi F.
      • Hoseini R.
      • Abedi M.
      • Montazeri A.
      Ultrasonographic features of uterine scar after laparoscopic and laparoscopy-assisted minilaparotomy myomectomy: a comparative study.
      ). Many studies have shown from radiological findings that uterine healing can be achieved after 3 months; however, it may not be achieved until 6 months (
      • Chang W.-C.
      • Chang D.-Y.
      • Huang S.-C.
      • Shih J.-C.
      • Hsu W.-C.
      • Chen S.-Y.
      • Sheu B.-C.
      Use of three-dimensional ultrasonography in the evaluation of uterine perfusion and healing after laparoscopic myomectomy.
      ;
      • Fujimoto A.
      • Morimoto C.
      • Hosokawa Y.
      • Hasegawa A.
      Suturing method as a factor for uterine vascularity after laparoscopic myomectomy.
      ;
      • Tsuji S.
      • Takahashi K.
      • Imaoka I.
      • Sugimura K.
      • Miyazaki K.
      • Noda Y.
      MRI evaluation of the uterine structure after myomectomy.
      ). These studies were inconclusive regarding the benefit to maternal outcome of delaying conception for more than 3 months in the case of post-surgical infection during pregnancy.
      To date there is a lack of any guidelines from international gynaecological associations about the optimal time from myomectomy to conception or the minimal time after surgery before attempting conceive. In this study, for those that specified a time interval, a third advised waiting between 3 to 6 months and more than a third between 6 and 12 months before attempting to conceive.
      The question of optimal time after myomectomy to attempt conception appeared relevant in our practice when confronting patients’ concerns about extending the time before attempting to conceive. As it is currently the gold standard treatment in the management of fibroids in infertile patients (
      • Khaw S.C.
      • Anderson R.A.
      • Lui M.-W.
      Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids.
      ), it remains difficult to advise couples about additional waiting time after myomectomy before they attempt to conceive. The articles available on post-myomectomy pregnancies do not provide subsequent details or explanations for a minimum protective period against the occurrence of obstetric complications (uterine rupture). As the literature has so far failed to provide an answer about an optimal time to avoid uterine rupture, this interval between surgery and conception is maybe not the answer, but rather other clinical factors (size and localization of fibroids, use of energy during the surgery, post-surgery complications) that are probably associated with an increased risk of uterine rupture, despite the fact it is a rare condition. However, this time factor could have a significant impact, as previously suggested (
      • Huberlant S.
      • Lenot J.
      • Neron M.
      • Ranisavljevic N.
      • Letouzey V.
      • De Tayrac R.
      • Masia F.
      • Warembourg S.
      Fertility and obstetrical outcomes after robot-assisted laparoscopic myomectomy.
      ). This review found that the time taken for women to conceive after a surgery was 17.6 months (mean) with a median time of 13.3 months (only one article reported the use of medical contraception to guarantee a specific time interval). Thus, for women who wanted to become pregnant, it happened more than 1 year after surgery. This is especially relevant in recent years, where almost half of women have delayed childbearing and have their first child during their 30s (
      • Nabukera S.K.
      • Wingate M.S.
      • Salihu H.M.
      • Owen J.
      • Swaminathan S.
      • Alexander G.R.
      • Kirby R.S.
      Pregnancy spacing among women delaying initiation of childbearing.
      ). At the same time, fertility rates begin to decrease, whereas age at myomectomy is a crucial determinant for achieving pregnancy, as infertility increases with age. Two studies evaluating the role of a woman's age on her odds of conception following myomectomy concluded that patients who were younger at the time of surgery were more likely to conceive (
      • Campo S.
      • Campo V.
      • Gambadauro P.
      Reproductive outcome before and after laparoscopic or abdominal myomectomy for subserous or intramural myomas.
      ;
      • Kasum M.
      Fertility following myomectomy.
      ). Furthermore, delaying pregnancy after a myomectomy increases the risk of uterine recurrence or further development of myomas with age, which could prevent women becoming pregnant (
      • Kotani Y.
      • Tobiume T.
      • Fujishima R.
      • Shigeta M.
      • Takaya H.
      • Nakai H.
      • Suzuki A.
      • Tsuji I.
      • Mandai M.
      • Matsumura N.
      Recurrence of uterine myoma after myomectomy: open myomectomy versus laparoscopic myomectomy.
      ).
      This extensive review allowed the selection and analysis of 80 articles grouping data from 3852 women who had had a myomectomy and who wanted to conceive. This large group size gives the study a strong external consistency and makes it clinically relevant to the topic. Finally, although it is limited by the evidence it provides, this is the first review on interval time between myomectomy and conception.
      There is a lack of accuracy and completeness of the data concerning the surgical procedures implemented and myoma characteristics. Some studies did not provide sufficient data about myomectomy (entering the uterine cavity, number of layer closures, post-operative complications such as infection of the operative site, size of the myoma, position of fibroids according to the FIGO classification), which provides insufficient power to determine the risk factors influencing the time interval from myomectomy to conception. However,
      • Koo Y.-J.
      • Lee J.-K.
      • Lee Y.-K.
      • Kwak D.-W.
      • Lee I.-H.
      • Lim K.-T.
      • Lee K.-H.
      • Kim T.-J.
      Pregnancy outcomes and risk factors for uterine rupture after laparoscopic myomectomy: a single-center experience and literature review.
      reported three cases of uterine rupture (included in this study) in their single-site study and compared them to those already published. No characteristics of the women associated with the occurrence of uterine rupture were identified. Like this study, the majority of ruptured cases occurred before labour (
      • Koo Y.-J.
      • Lee J.-K.
      • Lee Y.-K.
      • Kwak D.-W.
      • Lee I.-H.
      • Lim K.-T.
      • Lee K.-H.
      • Kim T.-J.
      Pregnancy outcomes and risk factors for uterine rupture after laparoscopic myomectomy: a single-center experience and literature review.
      ).
      Likewise, this review did not consider the position of fibroids due to the lack of data available. This is a factor which may have an impact on fertility, depending on whether the myoma is intramural or subserous, or if it is distorting the uterine cavity (
      • Tian Y.-C.
      • Wu J.-H.
      • Wang H.-M.
      • Dai Y.-M.
      Improved fertility following enucleation of intramural myomas in infertile women.
      ).
      There is a publication bias for uterine rupture, because it depends on whether these complications are reported or not, suggesting that the current findings could be underestimated. Also, data on post-operative complications such as infection of the operative site are missing in many studies, because it could be a factor influencing uterus healing after myomectomy, and then associated with infertility after myomectomy or severe obstetrical outcome.
      This study did not include hysteroscopic myomectomy as it is not the same procedure as laparoscopic or abdominal myomectomy: hysteroscopic myomectomy involves use of energy to remove all the fragments and is not performed for all myomas. Furthermore, the myometrium is not affected in the same way as it is with laparoscopic or abdominal myomectomy because hysteroscopic myomectomy does not require stitches regardless of the size of the myoma removed. But it must be remembered that uterine rupture during pregnancy may also occur after a hysteroscopic myomectomy (
      • Zeteroğlu Ş.
      • Aslan M.
      • Akar B.
      • Ada Bender R.
      • Başbuğ A.
      • Çalışkan E.
      Uterine rupture in pregnancy subsequent to hysteroscopic surgery: a case series.
      ).
      It is difficult to advise an optimal interval to provide a better chance of successful conception without uterine rupture. However, this review may provide some advice: active monitoring of the third trimester of pregnancy and perhaps no minimal time after myomectomy before trying to conceive. This is perhaps supported by the hypothesis that in the first trimester of the pregnancy the uterus has not grown as much and that the scar has enough time to heal to carry the pregnancy.
      There is no proof so far to recommend a minimum time interval between myomectomy and conception. An extended period did not seem to limit the risk of rupture, whereas several risk factors (number of layers, post-operative complications, size and number of myomas removed) may be involved in the occurrence of this rare complication (0.5% of all pregnancies in this study), close to the frequency of uterine rupture occurring in pregnancies following Caesarean delivery. Information about size and localization of myomas, use of energy, entering the uterine cavity, how many layers of stitches, and post-operative infection, appear to be mandatory in every surgery report, to facilitate the decision for the follow-up of a future pregnancy. Based on these results, individualization for each woman of a time interval after myomectomy before conception should be discussed. Complementary prospective data from a prospective trial focusing specifically on some major points that seem to be of clinical importance are mandatory to confirm the current results. Then, a trial comparing fertility, outcomes of pregnancy and delivery with a group of women with no minimal time to conception after myomectomy versus 3 months of waiting time after the surgery could be a matter of interest.

      Acknowledgements

      We gratefully acknowledge Sylvie Gautier for proofreading this manuscript.

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      Biography

      Dr François Margueritte is an obstetrician and gynecological surgeon. His fields of interest are gynecological surgery (oncologic or benign surgery) and clinical epidemiology.
      Key message
      There is insufficient evidence to advise a minimal time interval before attempting to conceive after myomectomy. Mean time from myomectomy to pregnancy is about 18 months. Risk of uterine rupture after myomectomy is minimal and not correlated with time interval from myomectomy to pregnancy.