Treatment of septate uterus

Abstract

Although there is insufficient evidence supporting the link between septate uterus and infertility, there are many studies demonstrated the effect of spetal incision on pregnancy in women diagnosed with septate uterus associated with infertility. Hysteroscopic metroplasty can significantly improve the reproductive performance of those with septate uterus. Some Müllerian malformations can be healed by surgery. The accurate diagnosis and appropriate therapeutic approch are fundamental for successful treatment. Any attempt at surgical correction of uterine abnormalities must be aimed at preserving or improving reproductive function. Among congenital uterine anomalies, septate uterus is the most amenable to simple hysteroscopic treatment. The resection of the septum is performed as standard treatment worldwide.

The most relevant indications for surgery of septate uterus are repeated abortion and infertility. With the advances in minimally invasive procedures, especially with the advent of hysteroscopy, other relative indications include infertility requiring special treatment by induction of ovulation, insemination, or other assisted reproductive technologies. Tomazevic T, et al^[1] have reported that the presence of septate uterus decreases the pregnancy rate and may increase the abortion rate after embryo transfers via in vitro fertilization/intracytoplasmic sperm injection. The negative impact of uterine anomalies on pregnancy and on live birth rates is an important deciding factors that should be considered when making the decision to treat uterine anomalies in infertile women. The literature^[2] has reported that prophylactic metroplasty could prevent adverse pregnancy outcomes, even in patients with no prior fertility problems. In recent years, there has been an increase in indications for treatment of conditions associated with primary infertility. It has also been suggested that metroplasty might be best performed during the “white balance” laparoscopy underteken before an assisted reproductive technique to prevent any potential obstetric accidents, especially in patients with long-standing infertility and declining fecundity (>35 years)^[3]. This paper aims to summarize the treatment of septate uterus and management of operation.

1. Overview of spetate uterus

Septate uterus is usually diagnosed during an infertility evaluation. The incidence of uterine septum is higher in the infertile population than the general population, which suggesst that there may be a connection with infertility^[4-7]. However, definitive proof of an association between septate uterus and infertility is lacking^[8]. A septate uterus may be partial or complete, and the septum may be thick or thin. There is also insufficient evidence to conclude that the length or width of the septum has a subsequent effect on pregnancy.

Nonetheless septate uterus does appear to affect reproductive health by impairing fertility, and increasing the likehood of adverse pregnancy outcomes^[4]. Compared with other uterine anomalies, septate uterus is associated with the highest incidence of reproductive failure and adverse obstetrical complications. It is also associated with the poorest reproductive outcomes such as abortion, preterm delivery and infertility, with fetal survival rates of 6% to 28% and a high rate of spontaneous miscarriage (>60%)^[9-11]. Others adverse pregnancy outcomes include intrauterine growth restriction, abnormal placentation, fetal malpresentation, and an increased risk of cesarean delivery^[2]. But there are many women with uterine septa who do not experience any reproductive difficulties^[12].

2. Pathophysiology of spetate uterus

Most women with Müllerian anomalies, particularly women diagnosed with septate uterus have good reproductive function, and only 20% to 25% may experience recurrent spontaneous abortions^{[9, 13]}.

There is limited evidence supporting the potential relationship between the pathophysiology of the uterine septum and impaired reproductive outcomes in women with a septate uterus. The argument behind resection of the septum is based on the hypothesis that the septum is composed of an entirely different structure than the normal uterine wall^[14-15]. Thus, embryo implantation into the septum would hypothetically, leading to a poorer reproductive outcome compared to implantation into the lateral uterine wall. To explain the negative impact of the septum on fertility and pregnancy outcomes, some studies^{[14, 16-18]} have suggested that the septum is a poor site for embryonic implantation due to the assumed poor vascularization, decreased sensitivity to preovulatory changes of the endometrium overlying the septum, uncoordinated contractility of the septum, or a local defect of vascular endothelial growth factor receptors in the endometrium covering the septal area.

Detti L, et al^[19] have reported that the implications of uterine subseptations for infertility and adverse pregnancy outcomes, may be the result of a combination of several factors such as a wide and misshapen uterine cavity, the subseptation length, and a decreased endometrial surface.

3. Treatment of spetate uterus

3.1. Changes in surgical techniques

The treatment of the septate uterus has undergone major changes, and many corrective surgical techniques have been proposed. Traditionally, the uterine septum is repaired with a laparotomy or hysteroscopic techniques.

The incisions of the uterine septum are first performed via laparotomy and hysterotomy and only in women with a history of repeated abortion. To preserve the ongoing pregnancy, noninvasive techniques such as bed rest, cervical cerclage, and tocolytic agents are frequently used. Abdominal metroplasty procedures performed have 3 types: the Jones technique, Bret-Tomkins metroplasty, and the El Mahgoub approach. The Jones technique involve transfundal uterine excision of the septate uterus by removing a cuneiform portion of the fundal myometrium and septum with subsequent repair^[20]. The Bret-Tomkins metroplasty is performed by division of the uterus in the anteroposterior plane and transverse division of the septum in the middle without excision of myometrial tissue. Both methods result in a viable pregnancies rate of 70% to 80%^[21-22]. The El Mahgoub approach used small fundal, transverse incisions in the uterus along the septum and the transfundal removal of the uterus with long scissors^[23].

The techniques have some complications including postoperative reduction of the uterine cavity, formation of postoperative adhesions, and inconveniences due to the peritoneal incision, such as the prolongation of the duration of hospitalization and a longer convalescence. Moreover, transabdominal metroplasty requires a postoperative interval of 3 to 6 months before conception, with a significant risk of uterine rupture in the subsequent pregnancy necessitating a routine cesarean section.

The development of the less invasive surgical hysteroscopy techniques has considerably simplified the therapeutic treatment. Therefore, these other invasive procedures have largely been abandoned. Resection of the septum improves reproductive outcomes. Hysteroscopic resection of the septum is safe and efficient and has become the primary modality of treatment. Currently, the preferred treatment for septate uterus is hysteroscopic metroplasty with good results^[12]. The advantages of this minimally invasive hysteroscopic approach are the following outpatient surgery with or without anesthesia/analgesia^[24], a reduced risk of intra- and postoperative morbidity, no risk of postoperative pelvic adhesions, and an increased rate of vaginal delivery^[25]. Hysteroscopic metroplasty can be performed in the operating room under anesthesia or in an office setting. The techniques used include incision of the septum with cold scissors and unipolar or bipolar cautery, or laser, or resection of the septum^[8]. Distending media for the uterus include saline, glycine, sorbitol, or mannitol, depending on the incision technique or the energy source. To date, there is insufficient evidence to recommend a specific instrument for the hysteroscopic incision of the septum^[8].

During the procedure, the tubal ostia are the surgical landmarks used for proper orientation. After clear vision of the cavity and its deformity is obtained, the septum is incised across the apex from the lower margin and is gradually reduced with progressive, upward, horizontal midline incisions until visualization of the muscular fibers is achieved. The incision of the septum is made equidistantly from the anterior and posterior uterine walls, and the procedure is completed when a restored triangular cavity occurs with free movement of the hysteroscopy between the 2 exposure of the muscle fibers of the fundus. Traditionally, the most commonly used instruments are the resectoscope fitted with an appropriately designed electrode and hysteroscopic scissors^[12].

After cervical dilatation, an electrode (monopolar or bipolar) is activated when the resectoscope is used. The cutting electrode usually applied is the 90°-angled electrode. With monopolar energy, the procedure takes longer, and there is a risk of complications of fluid overload^[26]. With bipolar energy, isotonic saline solution is used as the distention medium. Therefore, the risk of complications due to intravasation is lower than with monopolar energy. During resection, excessive bleeding or significant amounts of cellular debris may impair visualization of the surgical area and prohibit completion of the procedure ^[27-28].

Through the 5 or 7 French operative channel of an hysteroscopy, hysteroscopic cold scissors or energy modalities can be introduced to perform hysteroscopic metroplasty. Anesthetic time, recovery time, pain, and blood loss are reduced^[29-30]. Hysteroscopic metroplasty has the advantages of a shorter hospital stay, and patients are able to conceive within a shorter postoperative period^[31]. The absence of a postoperative uterine scar following transcervical metroplasty allows for labor and transvaginal delivery^[31]. It has been reported that hysteroscopic metroplasty may be performed in the office setting in some cases^[32-34], in particular when the septum is partial and thin and the procedure can be performed in an ambulatory surgical center. However, the unpredictable nature of this type of procedure demands caution and careful selection to avoid failure, frustration, and possible complications.Although hysteroscopic metroplasty for the septate uterus seems to be a relatively safe procedure, various complications can occur either during the procedure or in subsequent pregnancy and childbirth. To confirm the uterine contour, decrease the risk of uterine perforation, and assess complete removal of the septum and the presence of other anomalies, laparoscopy or transabdominal ultrasound may be used during hysteroscopic metroplasty^[11]. Concomitant laparoscopic or ultrasonic monitoring is an option to increase safety and security during hysteroscopic incision of the septum and may facilitate surgery by improving visibility of the surgical area. Other techniques for hysteroscopic metroplasty have been described, including the use of fluoroscopy, sonographically guided septal division, and even the tactile guidance of thin scissors^{[31, 35-36]}.

3.2. Different types of septate uterus

In 1996, Fedele L, et al^[37] reported that a residual uterine septum of <1 cm after hysteroscopic metroplasty does not adversely affect reproductive outcome. A cutoff length for the uterine subseptations by defining a uterus with a subseptation <10 mm in length as arcuate [American Fertility Society (AFS) class VI] and a uterus with a subseptation ≥10 mm in length as septate (AFS class V)^[38]. Therefore, surgical intervention was recommended for clinically important subseptations >10 mm. However, Detti L, et al^[19] found that when the subseptation was ≥5.9 mm in length, the postoperative cavity remodeling was independent of subseptation length. Thus, they proposed a new cutoff of ≥5.9 mm, stating that surgical correction restores a normal uterine cavity and thereby rectifies potential adverse implications of the septum.

A septate uterus with cervical septum (class U2C1) or double cervix (class U2C2) might also be present. Although there is no consensus on the incision of the cervical septum in these cases of septate uterus because of potential cervical weakness after surgery, incision of a coexisting cervical septum is usually performed ^{[11, 39-40]}. In cases of a double cervix and complete septate uterus, unification of the cavity is only performed from the level of the isthmus up to the fundus. Thus, incision of the cervical septum should be avoided because of potential trauma to the cervix, which is associated with cervical insufficiency in subsequent pregnancies.

3.3. Complications of hysteroscopic metroplasty

Hysteroscopic metroplasty may involve complications such as bleeding, fluid overload, uterine perforation, postoperative uterine adhesions, and uterine rupture in subsequent pregnancies.

When uterine distention is insufficient for providing adequate visualization of the septum to enable accompanying vessels from the uterine wall to be deflected from the central portion of the uterine septum, bleeding during hysteroscopic metroplasty may occur. Additionally, when the procedure is performed in the luteal phase of the menstrual cycle rather than in the early follicular phase, postoperative bleeding may also occur^{[36, 41]}. In the echo-guided procedure, however, bleeding is not a problem, as ultrasound is transmitted well through liquids and can be performed on any day of the menstrual cycle^[31]. Yet, echo-guided methods have been found to be less effective and precise than have been other methods. In addition, when the uterus is not distended, the patient may be exposed to significant intraoperative bleeding which may be difficult to control and may prohibit completion of the treatment in a single setting or stage.

When the duration of the operation is prolonged and the fluid deficit is not closely monitored, excessive fluid absorption may occur. This is very important, especially when monopolar instruments are used because the fluids used are devoid of electrolytes, potentially leading to hyponatremia^[42-44]. Candiani GB, et al^[45] have reported that there is a tendency for minimal central fundal adhesions to form at the base of the sectioned triangle, as contact between the unepithelialized surfaces is inevitable due to the wide area of the surgical resection.

To reduce the occurrence of intraoperative and postoperative complications, preoperative and postoperative management are important.To date, there is no consensus on the preoperative management of hysteroscopic metroplasty, and there is no evidence to support routine preoperative endometrial thinning. The rationale behind the use of agents to thin the endometrium prior to performing a hysteroscopy for septal incision is that hysteroscopic visualization may be improved when the procedure is performed early in the menstrual cycle or with endometrial suppression^[8]. In addition, medications used to thin the endometrium preoperatively usually create a hypoestrogenic environment which may increase the risk of postoperative adhesions forming. It recommend that hysteroscopic metroplasty be scheduled in the early proliferative phase of the menstrual cycle^[8]. In circumstances of a complete or a wide septum with narrow uterine cavities, preoperative endometrial thinning to facilitate visualization may be considered^[6].

To prevent reformation of the septum or intrauterine adhesions after metroplasty, many surgeons advocate the use of estrogen to rapidly epithelialize the denuded endometrial cavity^{[3, 46-48]}, or use temporary splints, such as intrauterine devices (IUD), to maintain distension of the uterine cavity^{[7, 44-49]}. Two studies^[50-51] have reported that IUD insertion and hormonal therapy after hysteroscopic metroplasty do not seem to help to prevent septal fusion. One randomized controlled trial^[6] comparing Foley balloon insertion versus no balloon insertion following hysteroscopic metroplasty has found that splinting the uterine cavity with a Foley catheter yielded no benefits for septum reformation, clinical pregnancy rate, or pregnancy outcomes.There is still no consensus on management after hysteroscopic metroplasty. Moreover, no benefit of routine antibiotic therapy during hysteroscopy has been established; however, many surgeons use routine antibiotic prophylaxis during hysteroscopic metroplasty.

After abdominal metroplasty, the margins of the endometrial lining are brought together when the uterine body is reconstructed ^[51].After hysteroscopic incision of the septum, however, wide areas in the endometrial covering are left on the anterior and posterior walls^[52].Candiani GB, et al^[45] assessed the appearance of the endometrium after incision of the septum with the correlated endometrial biopsy in 19 women who were randomized to follow-up hysteroscopy at different postoperative periods (1, 2, 4, or 8 weeks). Multiple biopsies at different intervals (7 d, 14 d, 1 month, and 2 months) after hysteroscopic septal incision in the 19 women were taken. At 2 months, the uterine cavity in each woman was almost normal with a minimal tendency to central fundal adhesions. Therefore, the authors concluded that perhaps there is no reason to delay attempts at pregnancy for more than 2 cycles after surgery. Another study^[53] evaluated the optimal waiting period for subsequent fertility treatment after metroplasty in 16 patients diagnosed with septate uterus.The research^[8] reported that 100% of patients by 2 months postoperatively demonstrated a healed uterine cavity. With respect to the time from incision of the septum to attempt of pregnancy, there is insufficient evidence to advocate a specific length of time before a woman should conceive.

After transcervical metroplasty, the rate of cesarean section is still high despite the avoidance of laparotomy. The label of “high-risk pregnancy” that has been attached to pregnant women with a history of hysteroscopic resection may explain this fact, making them more likely to receive intensive obstetric care^[30].

4. Conclusion

Although there is not sufficient evidence to indicate that uterine septum affects fertility, resection of the septum is performed worldwide as standard treatment in women experiencing repeated abortion. With the development of hysteroscopy techniques, the invasive procedures of laparotomy have largely been abandoned. Hysteroscopic resection of the septum has become the primary modality of treatment. However, hysteroscopic metroplasty may have complications, such as bleeding, fluid overload, and postoperative uterine adhesions, which require preoperative and postoperative management. More evidence is required for clinicians to reach consensus on the preoperative and postoperative management of hysteroscopic metroplasty and the specific length of time before a woman should conceive following hysteroscopic metroplasty.

Funding Statement

This work was supported by the National Key Research and Development Program of China (2018YFC1004800).

Conflict of Interest

The authors declare that they have no conflicts of interest to disclose.

AUTHORS’CONTRIBUTIONS

ZHANG Baiyu Conceptualized, drafted, and edited the manuscript; WU Susu Collected and analyzed the literature, conceptualized and submitted the manuscript; ZHAO Xingping Conceptualized and reviewed the manuscript; TAN Lin Analyzed and explicated the literature; XU Dabao Conceptualized the manuscript and supported for research funding. All authors have approved the final version of this manuscript.

Note

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