Platelet-rich plasma in the management of Asherman syndrome: case report

Fertility clinics worldwide are helping couples to achieve their goal of building a family. Infertility universally affects about 13% couples [1], and the etiology of the disease varies by region [2]. Asherman syndrome (AS) is defined as intrauterine synechiae developed in response to injury to the pars basalis of the endometrium most commonly after uterine instrumentation associated with pregnancy, such as curettage after miscarriage, postpartum bleeding, or retained placenta, as well as intrauterine surgery [3–7]. Tuberculosis is the most common infectious cause of intrauterine scarring worldwide, with poor response to treatment [8, 9]. AS is responsible for 7% cases of secondary amenorrhea in the USA [10]. The intrauterine adhesions can range from complete obliteration of the cavity to filmy, fluffy, or dense adhesions between uterine walls [7]. The main complications of the Asherman syndrome are infertility (43%) and impairment of menstrual flow, from oligomenorrhea to amenorrhea (62%) [11]. It was shown that 76% of patients after intrauterine adhesiolysis had new adhesion formation 1 month postoperatively, compared to 88% post-septum resection, 40% post-myomectomy, 0% post-polypectomy [12]. Current management approaches are directed towards the treatment and prevention of the subsequent intrauterine adhesion formation. The standard treatment is surgical, which involves lysis of intrauterine adhesions under direct hysteroscopic visualization, with the goal of restoration of the uterine cavity, as well as endometrial function and fertility [13, 14]. Prevention of re-scarring is achieved with mechanical measures such as intrauterine balloon or intrauterine device (with outcomes reportedly better with the balloon) and/or postoperative estrogen treatment [15–17]. After such combination treatment, some report almost 100% restoration of menses [18, 19]; however, achieving pregnancy is much more complicated and challenging, with post-treatment intrauterine pregnancy rate ranging from about 23 to 45% and live births from 28.7 to 32.1%, depending on severity of adhesions and female age [18, 20]. In those who get pregnant, there is an increased risk of serious complication such as placenta accreta or intrauterine growth restriction [3, 7, 11]. Hence, it is very clear that the current management of AS should ideally be directed not only towards removal of adhesions and prevention of their re-formation, but also towards the regeneration/revival of endometrial lining in order to provide a healthy layer of cells to support the pregnancy. Herein, we describe, to the best of our knowledge, the first reports on clinical use of platelet-rich-plasma (PRP) in the setting of Asherman syndrome. The goal of this publication is to report a potentially successful clinical application, which we are following up with a pilot randomized control study in our center. Patients signed informed consents after detailed discussions about the PRP treatment, with institutional IRB approval from University of California San Francisco in place. Case report #1 IO presented to us at age 34 with secondary amenorrhea. Her past gynecological history included prior long-term use of oral birth control pills (OCP) for contraception, with short period (3 months) of amenorrhea upon discontinuation, followed by a spontaneous pregnancy, which ended in an early pregnancy loss. Her pregnancy loss was managed by dilation and curettage (D and C), followed by two more D and C (sharp and suction curetting) for retained products of conception (POCs). Following the procedures, she had a few episodes of light-cyclic menstrual bleedings, but eventually developed amenorrhea. She reported that since her second D and C she had cyclic right lower quadrant pain and pressure, usually resolved with ibuprofen. Her past medical and family history was otherwise unremarkable. On our evaluation, she had normal hormonal profile (TSH, prolactin) and normal complete blood count. Transvaginal ultrasound demonstrated thin endometrial lining of 4.7 mm, with hyperechogenic tissue seen across the fundus, with very thin lining in lower uterine segment. Bilateral ovaries were of normal size, with total antral follicle count (AFC) of 8. Saline sonogram showed minimal uterine cavity distention, suggestive of intrauterine scarring. Repeat lining measurement after 2 weeks of exogenous estrogen demonstrated a thin endometrial stipe of 3.8 mm, with minimal interruptions. To address suspected AS, she had two hysteroscopies under general anesthesia with extensive lysis of adhesions, with postoperative intrauterine balloon placement and prolonged estrogen treatment both times. Resumed menses were light, and endometrial thickness increased to 5.4 mm in late proliferative phase, with luteal phase endometrial biopsy demonstrating good glandular development. She subsequently attempted spontaneous conception for 4 months and was unsuccessful. This was followed by four cycles of superovulation with aromatase inhibitors with intrauterine insemination without success, in which she was able to reach endometrial thickness of 6.3 mm. Repeat saline sonogram demonstrated very poor distention of uterine cavity, but no distinct intracavitary lesion. She subsequently underwent two additional office hysteroscopies with lysis of adhesions. At the last hysteroscopy, 1 ml of autologous platelet-rich plasma (PRP) was slowly infused into the uterine cavity through a Wallace IUI catheter at the very end of the procedure, after all hysteroscopic fluid was allowed to drain. PRP was prepared from patient’s peripheral blood by separation of platelets by centrifugation using Magellan Autologous Platelet Separator System (Isto Biologics, St Louis, MO). The catheter was slowly removed, and no leakage was noted. The patient tolerated the procedure well. Intrauterine balloon was placed to be removed after 7 days, while on antibiotic for 7 days and 4 mg of daily oral estradiol for 1 month (standard of care in our clinic). She remained in the dorsal position for 10 min prior to transitioning to recovery area. No postoperative pain or cramping was noted on the day of surgery or in the following days. Endometrial lining 2 weeks post-PRP infusion and on oral estrogen was still thin at 4.8 mm, and she underwent second PRP infusion, which was again uncomplicated. Her lining, however, was still thin at 5.0 mm 1 week after. The plan made with primary MD was to undergo an IVF cycle for embryo banking, with embryo transfer after improved endometrial lining, while option of using gestational carrier was discussed as well. However, while preparing for IVF cycle, the patient became spontaneously pregnant, now at age 37, with pregnancy in the third trimester at the time of this report.