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Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal de Poissy-Saint-Germain-en-Laye, 10 Rue du Champ Gaillard, Poissy 78300, France
Limoges University Hospital, Mother and Child Hospital, Department of Gynecology and Obstetrics and Reproductive Medicine, 8 Rue Dominique Larrey, Limoges 87000, France
Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal de Poissy-Saint-Germain-en-Laye, 10 Rue du Champ Gaillard, Poissy 78300, France
Limoges University Hospital, Mother and Child Hospital, Department of Gynecology and Obstetrics and Reproductive Medicine, 8 Rue Dominique Larrey, Limoges 87000, France
There is no proof of an ideal time interval after myomectomy to avoid uterine rupture.
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Mean time from myomectomy to pregnancy is about 18 months.
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Risk of uterine rupture is minimal after myomectomy.
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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.
). 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 (
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 (
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 (
FIGO Working Group on Menstrual Disorders FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age.
). 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 (
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.
). 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%) (
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 (
). Moreover, increasing the interval between surgery and conception may cause uterine fibroid recurrence, evaluated at between 34.2% and 41.6% at 3 years (
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 (
). 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) (
) 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 (
Reproductive outcome after laparoscopic myomectomy for intramural myomas in infertile women with or without associated infertility factors: laparoscopic myomectomy for myomas.
Patients’ age, myoma size, myoma location, and interval between myomectomy and pregnancy may influence the pregnancy rate and live birth rate after myomectomy.
A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.
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
Characteristic
n (%) 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 mentioned
1873 (64.8)
Instruction with time interval
878 (30.4)
Medical contraception during specified time interval
138 (4.8)
Interval time instructions from myomectomy to attempting to conceive (months) (n = 1016)
0<interval time<3
52 (5.1)
3≤interval time<6
345 (34.0)
6≤interval time<12
412 (40.6)
Interval time ≥12
207 (20.4)
Time from myomectomy to first pregnancy (n = 2889) (months)
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 2Distribution of mean time interval from myomectomy to pregnancy according to studies (n = 34).
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 [
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
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 (
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 3Distribution between gestational age at uterine rupture and time from myomectomy to pregnancy.
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
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
(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% (
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.
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 (
). 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
, 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 (
). Evaluation after abdominal versus laparoscopic myomectomy does not seem to demonstrate any difference in healing when evaluating the uterine scar with ultrasound (
). 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 (
). 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 (
), 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 (
). 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 (
). 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 (
). 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 (
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,
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 (
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 (
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 (
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.
References
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.
Reproductive outcome after laparoscopic myomectomy for intramural myomas in infertile women with or without associated infertility factors: laparoscopic myomectomy for myomas.
A comparison of the pregnancy outcomes between ultrasound-guided high-intensity focused ultrasound ablation and laparoscopic myomectomy for uterine fibroids: a comparative study.
Patients’ age, myoma size, myoma location, and interval between myomectomy and pregnancy may influence the pregnancy rate and live birth rate after myomectomy.
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.
Article info
Publication history
Published online: May 30, 2021
Accepted:
May 13,
2021
Received in revised form:
May 7,
2021
Received:
January 14,
2021
Declaration: The authors report no financial or commercial conflicts of interest.
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