Severe Ovarian Hyperstimulation Syndrome in a Woman With Breast Cancer Under Letrozole Triggered With GnRH Agonist: A Case Report and Review of the Literature

We report a rare case of ovarian hyperstimulation syndrome (OHSS) in a 28-year-old woman with breast cancer and with a history of polycystic ovary syndrome (PCOS) despite treatment with letrozole and gonadotropin-releasing hormone agonist (GnRH-a) triggering in a GnRH antagonist (GnRH-ant) protocol without the administration of any human chorionic gonadotropin (hCG) for luteal-phase support. The patient, who underwent controlled ovarian syndrome (COS)-oocyte cryopreservation before chemotherapy, required hospitalization. Complete recovery was achieved after treatment with volume expanders, human albumin, and cabergoline. Based on our case and literature review, it is possible to establish that estradiol (E2) modulation with letrozole and GnRH-a triggering does not eliminate the risk of OHSS. Furthermore, it is advisable to postpone GnRH-a depot to minimize the risk of OHSS after the suspension of letrozole, following menstruation or at least 7–8 days after triggering. It would be desirable to identify high-risk patients, also on a genetic basis, in order to avoid delays in oncologic treatments that could strongly impact life expectancy.

A multi-centre phase 3 study comparing efficacy and safety of Bemfola® versus Gonal-f® in women undergoing ovarian stimulation for IVF

Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm injection (n = 372) showed Bemfola yielding similar efficacy and safety profiles to Gonal-f. Women aged 20–38 years of age were randomized 2:1 to receive a single, daily, subcutaneous 150 IU dose of either Bemfola or Gonal-f. This study tested equivalence in the number of retrieved oocytes using a pre-determined clinical equivalence margin of ±2.9 oocytes. Compared with Gonal-f, Bemfola treatment resulted in a statistically equivalent number of retrieved oocytes (Bemfola 10.8 ± 5.11 versus Gonal-f 10.6 ± 6.06, mean difference: 0.27 oocytes, 95% confidence interval: -1.34–1.32) as well as a similar clinical pregnancy rate per embryo transfer in first and second cycles (Bemfola: 40.2% and 38.5%, respectively; Gonal-f: 48.2% and 27.8%, respectively). No difference in severe ovarian hyperstimulation syndrome was observed between treatment groups (Bemfola: 0.8%; Gonal-f: 0.8%). This study demonstrates similar clinical efficacy and safety profiles between Bemfola and Gonal-f, and suggests that Bemfola can be an appropriate alternative in ovarian stimulation protocols.

Severe ovarian hyperstimulation syndrome with GnRH agonist trigger during the COVID pandemic: lessons learned from an unusual case

Background: Injectable gonadotropins stimulate multi-follicular recruitment and allows retrieval of multiple oocytes for assisted reproduction. The widespread utilization of gonadotropin releasing hormone agonist (GnRHa) to induce oocyte maturation for oocyte retrieval has nearly eliminated the risk of severe ovarian hyperstimulation syndrome (OHSS), and only a few cases have been reported in the literature. The rarity of severe OHSS may lead to the mistaken conclusion that gonadotropin stimulation can be safely administered with limited monitoring, even in high-risk patients. We present an unusual case of a woman with limited monitoring due to the COVID pandemic who developed severe OHSS before GnRH agonist trigger and oocyte. Case Presentation: A 29-year-old nulliparous woman with polycystic ovarian syndrome (PCOS) initiated ovarian stimulation for oocyte retrieval. She had a robust initial response, and developed worsening abdominal pain, bloating, nausea, vomiting, and decreased appetite before retrieval. GnRH agonist was given to “trigger ovulation and retrieval scheduled due to the low reported incidence of severe OHSS. Symptoms progressed, and on the morning of retrieval, ultrasound demonstrated bilaterally enlarged ovaries >10cm and 48 oocytes were retrieved for a planned cryo-all cycle. She was hospitalized on the day of retrieval for severe OHSS and had two large-volume paracenteses. She was stable and discharged home by day 5, and symptoms markedly improved with the onset of menses. She has an ongoing pregnancy from her first frozen embryo transfer. Conclusion: We add a rare case of severe OHSS with a GnRHa trigger and cryo-all protocol with the onset of symptoms before GnRH agonist administration. Although rare, severe OHSS may still occur with a GnRHa trigger, and caution is needed when an initial robust response is identified. Here we also provide an opportunity to review the important patient risk factors for the development of OHSS and measures to reduce the risk in excessive responders.

Spontaneous Pregnancy with Severe Ovarian Hyperstimulation Syndrome Undergoing IVF-ET Cycle: A Case Report and Review

It is relatively rare that a natural spontaneous with severe ovarian hyperstimulation syndrome (OHSS) occurs undergoing in vitro fertilization and embryo transfer (IVF-ET).Pregnancy can cause OHSS to be delayed, and even lead to pregnancy loss in severe cases.In this case, we introduced the case of a 32-year-old female infertile patient with PCOS who underwent IVF-ET cycle and developed severe OHSS before embryo transfer. After volume expansion, symptomatic and supportive treatment and four times of abdominal puncture to extract ascites, the patient's condition is still protracted.However, interestingly, two weeks after giving up treatment, the patient found a spontaneous pregnancy and ended up with biochemical pregnancy. Severe OHSS was also gradually self-healing after biochemical pregnancy.This case emphasizes that pregnancy is one of the high-risk factors of OHSS, which can lead to the delay of the patient's condition with OHSS. Clinicians should be alert to the possibility of spontaneous pregnancy when they take luteal phase ovulation induction treatment undergoing IVF-ET cycle.