In Vitro Fertilization Cycle Outcomes for a Patient Undergoing Oocyte Retrieval following Ovarian Torsion

Abstract

Introduction:

To report a case of ovarian torsion following ovarian hyperstimulation with subsequent detorsion and oocyte retrieval.

Case Description:

The patient was diagnosed with torsion following acute onset abdominal pain following her leuprolide acetate trigger injection. The patient underwent diagnostic laparoscopy which confirmed right ovarian torsion. Following detorsion, the patient underwent oocyte retrieval as planned with 72 total oocytes and 70 mature oocytes retrieved. Thirty-six mature oocytes were cryopreserved; 34 were inseminated with conventional in vitro fertilization, of which 27 (79.4%) were fertilized. Sixteen blastocyst stage embryos were cryopreserved.

Discussion:

Ovarian torsion during ovarian hyperstimulation is a rare event, but consideration should be given to detorsion first, followed by oocyte retrieval. We demonstrate that mature oocytes can be retrieved even after temporary vascular compromise to the ovary with subsequent excellent fertilization and blastocyst conversion rates.

INTRODUCTION

Ovarian torsion is a gynecological emergency, requiring surgical intervention in order to detorse the ovary and salvage reproductive function.¹ Ovarian hyperstimulation for in vitro fertilization (IVF) is a risk factor for torsion as it leads to increased ovarian size, which can allow the ovary to rotate on the infundibulopelvic (IP) ligament and utero-ovarian ligament and become entangled.² The incidence in the general population of ovarian torsion is estimated at 2.7%, while the incidence of torsion following ovarian hyperstimulation syndrome (OHSS) is estimated at 16%.^3,4

The case presented here assesses the impact of ovarian torsion on cycle outcomes as measured by the number of viable oocytes retrieved, oocyte fertilization rate, and blastocyst conversion rate. We hypothesize that prompt ovarian detorsion would result in improved clinical outcomes.

CASE REPORT

The patient was a 34-year-old nulligravida woman who presented with 12-month history of infertility. The patient’s past medical history was notable for polycystic ovary syndrome (PCOS) and uterine fibroids having undergone an open myomectomy two years prior to presentation. The patient’s partner was a healthy 36-year-old male with no prior paternity nor any prior attempt at initiating a pregnancy with another partner. He reported normal energy and libido and denied erectile and orgasmic dysfunction. There was no history of testicular trauma, testicular tumor, or steroid use.

The patient and her partner both denied known family history of infertility, early menopause, recurrent miscarriage, stillbirth, learning disabilities, congenital anomalies, or genetic disorders.

The patient’s initial infertility workup was notable for an anti-Mullerian hormone level of 20 ng/ml, a pelvic ultrasound which showed multiple small intramural fibroids with no submucosal component, and polycystic ovarian morphology. The remainder of her evaluation was unremarkable with a day 3 lab follicle stimulating hormone (FSH) 8 IU/L, estradiol 51 pg/ml, Prolactin 22 ng/ml, thyroid stimulating hormone (TSH) 0.56 IU/ml, and hemoglobin A1c 5.5%. Her partner’s semen analysis was overall reassuring with a volume of 0.9 ml, concentration of 98.8 million/mL, 81% motility, and 7% normal forms.

The patient underwent ovarian hyperstimulation using an antagonist protocol. Ovarian hyperstimulation was initiated with recombinant FSH (Gonal-F, EMD-Serono) and human menopausal gonadotropin (HMG) (Menopur, Ferring Pharmaceuticals). The patient started on a dose of 150 IU FSH and 75 IU HMG. A gonadotropin-releasing hormone (GnRH)-antagonist (Cetrotide, EMD-Serono, 250 mg) was initiated on cycle day 8 to prevent ovulation. On cycle day 13, the patient’s peak estradiol level was 3039 pg/mL, with 10+ follicles noted on the right and left ovaries, and the patient was triggered with 40 units GnRH-agonist (leuprolide acetate, Abbott Laboratories). Estradiol levels below 3500 pg/ml are at low risk of OHSS.⁵ The patient was planned for a freeze-all cycle given her robust response, and due to personal reasons, preferred to freeze both oocytes and embryos.

The patient took her trigger shot 36 hours prior to her planned retrieval and called 24 hours after trigger shot reporting acute onset 10/10 right-sided abdominal pain. The patient felt waves of pain radiating to her back, legs, and right flank. Movement worsened her pain, but her pain improved on sitting still. The patient denied nausea, vomiting, and fever. The patient had no left -sided pain. The patient tried simethicone without relief.

The patient presented to the emergency department. Vitals were stable and within normal limits. Labs were sent and notable for white blood cells 11K/uL with 67% neutrophils. Her hematocrit was 40%, and other labs including electrolytes were normal. A computed tomography scan of the abdomen and pelvis demonstrated bilaterally enlarged ovaries consistent with hormonal stimulation and a normal appearing appendix. A pelvic ultrasound demonstrated bilaterally enlarged ovaries with color flow on Doppler bilaterally (Figure 1). On examination, the patient had tenderness in bilateral lower quadrants, right greater than left, with voluntary guarding.

Figure 1.

Pelvic ultrasound. (A) Left ovary and uterus. (B) Right and left ovaries. (C) Doppler flow to right ovary. (D) Doppler flow to left ovary.

Given enlarged ovaries, acute onset abdominal pain, tenderness on examination, and leukocytosis, the decision was made to proceed to the operating room urgently for diagnostic laparoscopy to evaluate for ovarian torsion. Abdominal entry was achieved via Veress needle. Initially two 5-mm ports were placed in bilateral lower quadrants. An additional 5-mm port was placed 8 cm lateral to the umbilicus on the right to facilitate manipulation of the large torsed ovary. Initial review demonstrated no intra-abdominal adhesions and normal upper abdominal survey.

Inspection of the pelvis showed the right ovary to be torsed once around the IP ligament, and was detorsed using a blunt-tipped grasper. In trying to detorse the ovary, the ovarian cortex was noted to be friable, and 2 – 3 punctures were incidentally made. The ovary was ultimately placed in its anatomically correct position and the inferior aspects of both ovaries were placed under the uterus. The left ovary was enlarged but normal in appearance and was not torsed.

The patient felt well and had complete pain relief following the detorsion and was discharged home. The patient did not receive venous thromboembolic prophylaxis perioperatively as she was in a low-risk category, and the literature shows no increased risk of venous thromboembolism following ovarian detorsion.⁶ The patient returned the following day for her scheduled oocyte retrieval. Both ovaries appeared normal on ultrasound at the time of her retrieval. Seventy-two total oocytes were retrieved, 70 of which were mature (metaphase II [MII]). Thirty-six MII oocytes were cryopreserved and 34 were inseminated with conventional IVF with a 79.4% fertilization rate (27/34). Sixteen blastocyst stage embryos were cryopreserved.

DISCUSSION

Ovarian torsion is a gynecologic emergency as it poses risk to ovarian viability and threatens reproductive potential in the future. The incidence of ovarian torsion is unknown, but it is classically reported as the fifth most common gynecologic emergency. The diagnosis is clinical, with supportive laboratory and imaging findings that can help providers make the diagnosis.

Clinical findings include nausea and vomiting, pelvic and lower quadrant tenderness, peritoneal signs on abdominal examination, and adnexal tenderness on pelvic examination.⁷ Laboratory findings that can raise concern include leukocytosis and in severe cases, elevated lactate levels.⁷

Findings on pelvic ultrasound that support the diagnosis include a unilaterally enlarged ovary, peripheralization of ovarian follicles, ovarian stromal edema, absence of color doppler blood flow to the ovary, free pelvic fluid, and displacement of the ovary from its usual anatomic location.^8,9 There have been clinical tools developed to estimate pre-operative probability of true torsion, which found ovarian size, neutrophil to lymphocyte ratio, and nausea/vomiting were the best predictors of torsion, but these had low overall specificity and sensitivity.^10,11

Risk factors for ovarian torsion include the presence of an ovarian mass or enlarged ovary. As such, ovarian hyperstimulation leading to enlarged ovaries with multiple follicles is a risk factor. The incidence of ovarian torsion during ovarian hyperstimulation is estimated at 2.1%.^12,13

More often, torsion is diagnosed after oocyte retrieval, possibly due to movement of the ovary by the surgeon when aspirating the follicles. Regardless of the timing of ovarian torsion, any concern for this diagnosis should lead to emergent evaluation given the risk of vascular compromise to the ovary.

There are limited reports of oocyte retrieval following ovarian detorsion in the literature. Smith et al. describes a 27-year-old patient whose husband carried a balanced translocation who presented on cycle day 11 (one day after trigger shot administration) with signs of right ovarian torsion.¹⁴ Transvaginal ultrasound identified decreased right ovarian venous flow but preservation of right ovarian arterial flow. The patient underwent emergency laparoscopic right ovarian detorsion followed by previously scheduled oocyte retrieval 36 hours following trigger shot on postoperative day 1. Ten oocytes were retrieved from the right detorsed ovary, 4/10 (40%) oocytes fertilized normally, and 3/4 (75%) zygotes developed to blastocyst stage. Fifteen oocytes were retrieved from the left ovary, 14/15 (93%) were fertilized and 9/14 (64%) zygotes developed to blastocyst stage. Of note, maturity rates were not reported so fertilization rate could not be confirmed.

Robson et al. also described a presentation of a 37-year-old patient undergoing IVF for male factor infertility for acute torsion following trigger shot injection.¹⁵ The patient presented 35 hours post trigger with severe abdominal pain and underwent immediate oocyte retrieval prior to detorsion. They report a poor fertilization rate of 33% from the left ovary that was torsed, and 75% from the unaffected right ovary. Similarly, Stefunidis et al. described a case involving a 33-year-old undergoing IVF for male factor infertility who presented with acute ovarian torsion following trigger shot injection.¹⁶ The patient received the trigger shot on cycle day 13, presented with symptoms on cycle day 14, and was observed until cycle day 15 when the patient showed signs of peritonitis. They proceeded with retrieval prior to ovarian detorsion with no oocytes retrieved from the affected side. Her pain did not resolve after retrieval, so the patient then required laparoscopy with ovarian detorsion. In a different management approach, Inoue et al. describe performing ‘follicular aspiration for volume reduction’ for a 34-year-old patient with unexplained fertility who presented with presumptive torsion prior to oocyte retrieval.¹⁷ They aspirated a 58 mm x 24 mm simple right ovarian cyst when the patient presented with right adnexal pain. The cyst fluid was evaluated microscopically, but no oocytes or cumulus cells were found. They then administered a trigger shot and retrieved oocytes 35 hours later. Fifteen MII oocytes were retrieved; six from the affected right ovary and nine from the left ovary. Fourteen oocytes fertilized (reported 93% fertilization rate), with eight cryopreserved at 2 pronuclear (2PN)-stage and six cultured to blastocyst-stage. Two blastocysts were cryopreserved. The patient’s pain reportedly resolved after follicular aspiration. As such the patient never underwent laparoscopy, so torsion was never confirmed.

Our case is most similar in management strategy to Smith et al., with ovarian detorsion performed prior to scheduled oocyte retrieval. However, our case was remarkable for the number of oocytes retrieved and the high fertilization rate. This may be due to a more rapid restoration of ovarian blood flow (time from initial patient phone call to operation was 5 hours), or due to the good prognosis nature of our patient (young age with good ovarian reserve). Interestingly, women with PCOS have lower fertilization rates than age-matched controls,¹⁸ so our patient’s outcome is especially reassuring. Pregnancy outcomes have not yet been collected for this case as transfer was delayed by the patient for personal reasons. This additional data would have been useful in assessing if ovarian torsion pretransfer affects pregnancy outcomes. However, it is reassuring that the patient had 16 high quality blastocysts cryopreserved.

The rationale behind detorsing the ovary initially, followed by retrieval, is that this approach minimizes the interruption of blood flow to the developing follicles, thus reducing the risk of hypoxic injury to the oocytes. In the general population, the classic management of ovarian torsion with a nonviable appearing ovary was oophorectomy, as the theoretical risks of detorsion included emboli and sepsis if necrotic tissue was left in place.¹⁹ However, multiple observational studies have shown that even an ovary that appears nonviable at the time of surgery will often regain some function as assessed by follicular development on ultrasound.^20,21 Immediate retrieval prior to detorsion, as reported by Robson et al. and Stefunidis et al. is arguably faster than performing a diagnostic laparoscopy; however, this approach is only possible if patients present with ovarian torsion approximately 35 – 36 hours after receiving their trigger shot. These two reports do not state the time from onset of symptoms to retrieval and detorsion, but if patients present with torsion less than 36 hours following trigger, as our patient did, then immediate detorsion followed by oocyte retrieval at the planned time is indicated. It is possible that the fewer mature oocytes and resultant 2PN zygotes obtained in these two studies were due to a long time period between torsion and retrieval.

CONCLUSION

In conclusion, our case demonstrates that good outcomes following oocyte retrieval are possible following ovarian torsion. Prompt detorsion, followed by oocyte retrieval as scheduled, led to adequate oocytes being retrieved with no impact on oocyte competence as reflected by normal maturity, fertilization, and blastocyst conversion rates.