Fertility preservation in women with placenta accrete spectrum undergoing organ-sparing surgery

The realization of the female's reproductive potential is a natural human need. Radical organ-removing surgery is a direct barrier to reproduction and is a serious medical, social and demographic problem [1]. The placenta accreta spectrum is one of the leading causes of hysterectomies in women of reproductive age worldwide, with a current incidence rate of about 0.17% (1:588). It is steadily increasing [2, 3] due to the significant increase in the number of caesarian deliveries, which is a major risk factor for abnormal placental implantation and invasion into the uterine scar [4, 5]. More than half of operations for placenta accreta spectrum worldwide end in hysterectomy resulting in the loss of reproductive function [6, 7]. Uterine transplantation has recently emerged [8, 9] is still not a routine operation and remains an experimental treatment [10].

Innovative organ-sparing surgical techniques such as fundal transverse cesarean section with metroplasty and excision of the area of abnormal placental invasion [11, 12], which has been performed at the V.I. Kulakov NMRC for OG&P since 2014, offer significantly better chances of maintaining normal menstrual and reproductive function in patients with placenta accreta spectrum. Such surgical modalities have been developed due to modern proprietary techniques of surgical hemostasis, such as bilateral ligation of the internal iliac arteries, temporary occlusion of the common iliac arteries, and complex compression hemostasis [13, 14].

To date, 393 organ-sparing operations for the placenta accreta spectrum have been performed at the National Centre in pregnant women from different regions of Russia. Despite the expansive geography of the patients, the staff of the Centre continues monitoring their health not only in the early but also in the distant postoperative period, including monitoring the course and delivery of subsequent pregnancies. The latter is highly challenging due to the lack of accumulated international experience in managing and delivering women with a history of placenta accreta spectrum and organ-sparing surgery [15–17].

Results

Due to the remoteness of the regions, determining the actual number of pregnancies after organ-preserving treatment and metroplasty for the placenta accreta spectrum can be challenging. We analyzed the course and outcome of pregnancies in patients after organ-sparing surgery for morphologically confirmed placenta accreta spectrum, conducted at the V.I. Kulakov NMRC for OG&P. The study was approved by the Ethical Committee of the Centre.

We analyzed medical history, clinical characteristics, and results of laboratory and diagnostic investigations of 9 patients who had pregnancies after metroplasty morphologically confirmed placenta accreta spectrum and medical records of 6 newborns. Ultrasound examination was performed on Voluson S6 Expert (GE Healthcare, Austria) and SAMSUNG MEDISON WS80A (Samsung Medison, South Korea) expert class systems using 3D\4D transabdominal convex multi-frequency (2–8 MHz) and 3D\4D intracavitary multi-frequency (5–13 MHz) probes (Fig. 1). Placental and myometrial tissue fragments were fixed for 24 hours in a 10% formalin buffered solution. Histological (hematoxylin and eosin staining) and Van Gieson's picrofuchsin (muscle tissue stained yellow and connective tissue stained red) were performed on serial paraffin sections.

Between 2014 and 2021, 9 patients who underwent organ-preserving surgery for the placenta accreta spectrum reported pregnancy. Their medical history and clinical characteristics are presented in Table 1. Five patients had multiple comorbidities, including chronic arterial hypertension, diabetes mellitus, anemia in pregnant women, kidney, liver, heart, and vascular disease, and bronchial asthma.

Worth noting is a high parity in this group of patients. Only one patient had her third pregnancy; 5 patients had 4 to 7 prior pregnancies; 3 had from 8 to 13 pregnancies and complicated obstetric-gynecological history. A total of 10 pregnancies were recorded in the study group; their specific course and outcomes are given in Table 2.

Consecutive pregnancy occurred one year after organ-sparing surgery in 5 patients, 3 patients after two years, and one after three years.

Only one patient was diagnosed with a Cesarean scar pregnancy and underwent a surgical termination at nine weeks. One patient had two pregnancies during the follow-up period that ended in spontaneous abortion at 5 and 20 weeks. One patient had an ongoing uncomplicated pregnancy at the time of publication of the study, with a gestational age of 16 weeks.

Of the six pregnancies that ended in delivery, in one case, there was operative emergency delivery at 33 weeks performed at the patient's place of residence for hemorrhage and suspected fundal scar dehiscence. Outpatient follow-up of 5 patients was performed at the V.I. Kulakov NMRC for OG&P. During the follow-up, 2 patients were diagnosed with moderate pre-eclampsia and late fetal growth restriction, but no clinical or ultrasound signs of scar dehiscence or placental accreta spectrum were found in any of the patients (Fig. 1).

All five patients delivered routinely at 37–38 weeks' gestation at the V.I. Kulakov NMRC for OG&P (Fig. 2). No clinical signs of uterine scar dehiscence were observed at surgical delivery (Fig. 2B).

Histological examination of myometrium samples of the post-metroplasty lower uterine segment stained with hematoxylin and eosin, taken after cesarean section, was performed and compared with myometrial samples taken from the area outside the area of invasion and dense attachment, where no metroplasty was performed. The myometrium in the metroplasty area showed no signs of thinning or defects (Fig. 3), separated by thin interlayers of connective tissue, as confirmed by Van Gieson's picrofuchsin staining for connective tissue (Fig. 3); blood vessels of various diameters were present, with no thickened wall. This histological pattern was consistent with an uncomplicated pregnancy without significant tissue architectonics abnormalities. Histological examination of the myometrium in the area of the previously performed metroplasty confirmed that its structure was comparable to that of myometrium without placental invasion (Fig. 3). Thus, the myometrium samples after metroplasty with the restoration of the uterine wall integrity corresponded to myometrium with regular architectonics of smooth muscle fibers, a moderate number of vessels, the amount of connective tissue was not significantly increased. There were no signs of invasion and dense attachment, i.e., myometrium was comparable to myometrium without abnormal placentation. The postoperative period was without complications in all cases.

Samples of myometrium: A ×40; C, E ×100 without metroplasty; B ×40; D, F ×100 after metroplasty; (A–D – stained with hematoxylin and eosin; E, F ×100 – stained with Van Gieson picrofuchsin (for connective tissue), red – connective tissue septa; light brown – myometrium, ×100 (marked with arrows). Asterisks indicate the vessel lumen

Conclusion

In this pilot study of 10 pregnancies in 9 patients who underwent organ-sparing surgery for morphologically confirmed placenta accreta spectrum in a previous pregnancy, recurrent pathological chorionic invasion into the scar was detected in one patient. Of the six pregnancies that ended in delivery, most patients delivered as planned and had no hemorrhagic complications or clinical and histological signs of myometrial dehiscence. Despite a complicated obstetric history and a high incidence of complications, such as spontaneous miscarriage, preeclampsia, fetal growth restriction, and anemia, six patients gave birth to live-viable babies. Further research is needed to assess the factors influencing the development of complications and to develop predictive algorithms and methods to improve pregnancy outcomes in post-metroplasty patients.