During the follow-up period, 52 women achieved 53 pregnancies (25 pregnancies in the non-CDMs group and 28 pregnancies in the CDMs group; one woman from the CDMs group achieved two pregnancies). Eight of these pregnancies arose following IVF. The overall pregnancy rate was 68.42% (52/76), the overall spontaneous pregnancy rate was 57.89% (44/76), and the postoperative infertility rate was 38.16% (29/76). Of these women, two had twin pregnancies following IVF. Moreover, 38.16% (29/76) of women still suffered from infertility after myomectomy.
The postoperative infertility rate (50.00% vs. 23.53%, t = 5.579, P = 0.018) was significantly higher in the non-CDMs group than that in the CDMs group [Table 2]. Furthermore, the spontaneous pregnancy rate was significantly lower in the non-CDMs group than that in the CDMs group [Table 2]. Among the pregnant women, the live birth rate (88.00% vs. 64.29%, t = 4.012, P = 0.045) was significantly higher in the non-CDMs group than that in the CDMs group [Table 2]. Regardless of whether women underwent induced abortion after myomectomy due to social factors (two in the non-CDMs group and one in the CDMs group), the postoperative adverse pregnancy outcome rate in the non-CDMs group was significantly lower than that in the CDMs group [Table 2].
The mode of delivery (vaginal delivery or cesarean delivery) was not significantly different between the two groups [Table 2]. However, the rate of cesarean section indication as a result of a previous history of myomectomy was significantly lower in the non-CDMs group than that in the CDMs group [Table 2]. During selective cesarean sections, two women in the non-CDMs group were identified as possessing previous myomectomy uterine scars with defective impairment, as evidenced by thinning of the membrane. However, due to timely cesarean section, both mothers and their babies were safe.
The premature labor rates (9.09% vs. 11.11%, P = 1.000), placenta accrete rates (0% vs. 11.10%, P = 0.382), postpartum hemorrhage rates (4.50% vs. 5.60%, P = 1.000), premature rupture of membranes rates (13.64% vs. 16.67%, P = 1.000), fetal distress rates (9.09% vs. 0%, P = 0.560), and uterine dehiscence rates (9.09% vs. 0%, P = 0.560), were not significantly different between the non-CDMs and CDMs groups.
Postoperative pregnancy outcomes did not differ significantly according to myomas of different sizes [Table 3]. When patients were classified according to the surgical approach undertaken, we observed that postoperative pregnancy outcomes were not significantly different between the two groups of women; although, pregnancy rate was significantly higher in the TAM group than that in the LM group [Table 3]. Additional analysis showed that the rate of CDM (25 [52.1] vs. 13 [37.1], P = 0.177), myoma number (2 [1–2], 1 [1–2], P = 0.148), largest myoma diameter (7 [5.3–8.0] cm, 6 [5.0–7.0] cm, P = 0.050), and age (32.48 ± 4.15 years vs. 32.66 ± 4.12 years, P = 0.847) were not significantly different when compared between the TAM group and the LM group.
A total of 29 patients still suffered from infertility following myomectomy. Cox regression showed that preoperative duration of infertility, type of infertility, BMI, myoma number, myoma size, myomectomy approach, and whether the myoma penetrated into the uterine cavity or not during myomectomy, were not identified as risk factors for subsequent fertility. Compared with non-CDM, CDM was identified as a risk factor for fertility. Following the enucleation of CDM, the postoperative risk of infertility was 0.269 times lower than enucleation of non-CDM (risk ratio [RR] = 0.269, 95% confidence interval [CI]: 0.930–0.779, P = 0.015). For every 1 year increase in age, the postoperative risk of infertility increased by 1.141 times (RR = 1.141, 95% CI: 1.005–1.295, P = 0.041).
Until the end of the follow-up period, three patients were using contraception (two women had given up their desire for fertility due to social factors, whereas the third underwent the second myomectomy due to relapse, and planned to try to conceive after an appropriate interval on contraception from the time of the second surgery
For over a decade, there has been great debate on the link between intramural myoma and fertility, and few studies have attempted to address this association. The main debate rests on whether CDM adversely affects fertility to a greater degree than non-CDM.
In this study, the clearly higher pregnancy rate, spontaneous pregnancy rate, and reduced rate of infertility provided strong evidence that the enucleation of intramural myomas plays an important role in fertility improvement in women with unexplained infertility and intramural myomas. However, we had no specific control group featuring women with unexplained infertility and intramural myomas, who did not undergo myomectomy; consequently, it is not clear how important the role of myomectomy is in terms of improving infertility. However, the significantly higher postoperative pregnancy rate and lower postoperative infertility rate observed in this study demonstrated that intramural myomas do adversely affect fertility.
Compared with the non-CDMs group, the lower postoperative infertility rate, and higher postoperative spontaneous pregnancy rate in the CDMs group clearly show that CDM adversely affects fertility to a greater extent and that more benefit can be gained after the enucleation of CDM in women with unexplained infertility. Among the postoperative pregnant women, the greater incidence of adverse pregnancy outcomes in the CDMs group showed that even though enucleation of CDM might improve fertility to a greater extent, this type of surgery might damage the myometrium or endometrial receptivity such that more pregnancies result in adverse outcomes.
Myoma size, and the type of surgical approach were not identified as factors affecting fertility; this result concurred with our previous study. Furthermore, the pregnancy rate was significantly higher in the TAM group than that in the LM group, although there was no significant difference between these two types of surgical approach in terms of myoma number, myoma size, age, and whether the uterine cavity was distorted or not. The reason for why the TAM group resulted in a higher pregnancy rate remains unclear, although this might be attributable to the slightly larger myoma diameter in this group of women (7 [5.3–8.0] cm, 6 [5.0–7.0] cm, P = 0.050) in the TAM group.
Cox regression analysis showed that the postoperative rate of infertility in the CDMs group was 0.269 times lower than that in the non-CDMs group. Enucleation of CDM yields more benefits for women with unexplained infertility; this might be because CDM damages the uterine cavity volume in a more obvious manner compared with non-CDM, and that enucleation restores a normal uterine cavity. Enucleation of non-CDM patients might still be beneficial to fertility because intramural myomas might impair fertility by limiting embryo or semen transport, causing endometrial atrophy or inflammation, or by interfering with implantation. This study is supported by the work of Pritts et al. who performed a systematic literature review and meta-analysis and concluded that intramural myomas are associated with a lower pregnancy rate and live birth rate, as well as non-CDMs. Nevertheless, a recent publication showed that the enucleation of myomas causing distortion of the uterine cavity can significantly improve live birth rate from 23.3% to 52.0% in subsequent pregnancies, and that reservation myomas, which do not cause distortion of the uterine cavity can achieve a high live birth rate that is similar to women without myomas. This suggested that CDM adversely affects fertility in an obvious way, while non-CDM does not. Unfortunately, this previous study lacked a control group of women with CDM who did not undergo surgery. Similarly, Somigliana et al. conducted a prospective controlled study, which showed that non-CDM with a diameter less than 5 cm did not impact on the success of IVF procedures. However, it is difficult to conclude that non-CDM has no adverse impact on fertility from the data presented in this previous publication because the study involved women with subserous myomas, which have a little adverse impact on fertility.
In this study, the overall pregnancy rate was 68.42% and the spontaneous pregnancy rate was 57.89%; these data concurred with a previous publication which showed that 74.00% of infertile women finally conceived after myomectomy. Thus, it is advisable to suggest to women with unexplained fertility and intramural myomas that they undergo myomectomy to improve their fertility, especially for women with CDM.
The data also show that the live birth rate was lower, and the adverse pregnancy outcome rate was higher, in the CDMs group than those in the non-CDMs group. This might be due to the fact that surgery involving enucleation of CDM is more difficult than non-CDM. During the operation, the fallopian tube and endometrium might be adversely influenced, thus resulting in a slightly higher ectopic pregnancy rate and miscarriage rate in the CDMs group.
As to the delivery mode, the higher rate of cesarean sections at the sole indication of a history of the previous myomectomy in the CDMs group was attribute to the over-concern of obstetricians and patients with regards to uterine rupture during vaginal delivery. The low uterine dehiscence rate, and obstetric complications rate, should serve as a reminder for obstetricians and patients that a history of myomectomy is not an absolute indication for caesarean section.
With regards to risk factors for postoperative infertility, the present results clearly show that the postoperative infertility rate increased with age. Sunkara et al. also showed that the adverse effects of intramural myomas on fertility was even greater when women were younger than 37 years. Furthermore, Borja de Mozota et al. conducted a study including 297 infertile women with myomas, and demonstrated that age (over 35 years, RR = 2.450) was a negative factor for fertility.
This study was limited by the fact that we had no control group of women with unexplained infertility and intramural myomas who did not undergo surgery. Consequently, we cannot state with absolute conviction that the enucleation of intramural myomas improves fertility. However, to include this type of control group in this study would have been ethically controversial because that the ability to restore postoperative fertility declined with age (RR = 1.141, 95% CI: 1.005–1.295, P = 0.041) and the infertile couples are desperate to undergo such surgery to achieve spontaneous pregnancy, or seek IVF.
In conclusion, irrespective of whether intramural myomas distort the uterine cavity or not, they can exert an adverse effect on fertility. Women with unexplained infertility and intramural myomas have a better chance of conception after myomectomy, particularly those with CDM. Since postoperative improvement in fertility declines with age, conservative surgery should not be postponed for a long period.
Financial support and sponsorship
This study was supported by grants from Beijing Municipal Science and Technology Commission (No. Z111107058811031 and No. Z131107002213090), and Beijing Obstetrics and Gynecology Hospital, Capital Medical University (No. fcyy201613).
Conflicts of interest
There are no conflicts of interest.
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Edited by: Peng Lyu
Keywords:© 2017 Chinese Medical Association
Infertility; Myoma; Pregnancy Outcome; Uterine Myomectomy