A multi-centre randomised controlled trial comparing megestrol acetate to levonorgestrel-intrauterine system in fertility sparing treatment of atypical endometrial hyperplasia.

PURPOSE: The objective of the trial was to compare the regression rate of atypical endometrial hyperplasia (AEH) in patients treated with megestrol acetate (MA) vs. levonorgestrel-intrauterine device (LNG-IUS). We also aimed to assess the fertility and pregnancy outcomes in these patients. METHODS: The study was a phase II multi-centre randomised controlled trial on the use of MA compared to LNG-IUS in the treatment of AEH conducted from January 2020 to January 2024 in Singapore. Women who were diagnosed with AEH and between 21 and 40 years old were included. The patients were randomised to receive either MA (160 mg orally daily) or LNG-IUS. The primary outcomes assessed were the regression rates at 3 months, 6 months and 9 months of treatment. The secondary outcomes assessed were the side effects, patient acceptability and fertility outcomes. RESULTS: Thirty-six patients completed the trial. The overall regression rate was 88.9% by 9 months. There was no statistically significant difference in the 9-month complete regression rate between MA vs. LNG-IUS. There was also no significant difference in side effects and weight change between both arms. Nineteen patients were actively pursuing fertility after complete regression. There were 8 pregnancies achieved, with resultant 4 live births and 4 miscarriages. CONCLUSION: Our study confirms a high regression rate of AH with medical treatment. LNG-IUS is a non-inferior treatment compared to megestrol acetate. Successful pregnancy outcomes can be achieved after regression of AEH. Long-term studies of sufficient sample-size are needed to assess for fertility and pregnancy outcomes, risk of recurrence and long-term risk of malignancy. TRIAL REGISTRATION NUMBER: The study was registered with the Health Science Authority (HSA) (License No.: CTA1900087) on September 5, 2019: https://eservice.hsa.gov.sg/prism/ct_r/enquiry.do?action=loadSpecificDetail . The trial was registered retrospectively on ClinicalTrials.gov (ID: NCT05492487) on April 7, 2022: https://clinicaltrials.gov/study/NCT05492487 .

The Effect of Luteinising Hormone Suppression in In Vitro Fertilisation Antagonist Cycles.

Use of GnRH antagonists in IVF stimulation protocols shortens controlled ovarian hyperstimulation (COH) and reduces the risk of ovarian hyperstimulation syndrome (OHSS). However, profound reduction in LH levels has been associated with use of GnRH antagonists. This study aims to determine if LH suppression during GnRH antagonist cycles results in poorer IVF outcomes. This was a prospective pilot longitudinal study where serum LH levels were measured on day 2/3 of the menstrual cycle before COH, 1/2 days following institution of GnRH antagonist and at the day of ovulation trigger. A threshold of LH <0.5 IU/L was used to define profound LH suppression. Data on IVF outcomes was collected. Logistic regression analysis was used to investigate risk factors associated with LH suppression following GnRH antagonist IVF treatment. Ninety-one eligible women were recruited. Women underwent a standard antagonist cycle with Puregon 200u and Ganirelix. No participant had LH <0.5 IU/L prior to GnRH antagonist treatment, and 27 participants (29.7%) had significant LH suppression at either time point. Predictors of profound LH suppression following GnRH antagonist treatment identified (P < 0.20) were age (OR = 0.80, P = 0.013), no previous ovulation induction (OR = 0.26, P = 0.033) and previous GnRH antagonist IVF cycle (OR = 4.32, P = 0.125). Numbers of oocytes, embryos and ongoing pregnancy rates at 12 weeks gestation in patients with and without LH suppression did not differ significantly. We found associations between clinical characteristics and risk of profound LH suppression in women undergoing GnRH antagonist IVF cycles, but no significant differences in IVF and pregnancy outcomes between women with and without significant LH suppression.

Laparoscopic Tubal Re-anastomosis or In Vitro Fertilisation in Previously Ligated Patients: A Comparison of Fertility Outcomes and Survey of Patient Attitudes

INTRODUCTION: We aim to compare live birth rates, cost analysis and a survey of patient attitudes between laparosopic tubal re-anastomosis and in vitro fertilisation (IVF). MATERIALS AND METHODS: A retrospective study was done in a single reproductive medicine and IVF unit in Singapore from January 2011 to December 2016. Previously ligated patients underwent either laparoscopic tubal re-anastomosis or IVF. The primary outcome was first live birth after treatment. Interval to first pregnancy, miscarriage and ectopic pregnancies were also reported. Patients attending the subfertility clinic completed a questionnaire on IVF and tubal re-anastomosis on preferred choice of treatment, before and after reading an information sheet. RESULTS: Twelve patients underwent tubal re-anastomosis while 31 patients underwent IVF treatment. Pregnancy (75.0% vs 35.5%) and live birth (58.3% vs 25.8%) were significantly higher in the tubal surgery group (P <0.05%) after transferring all available embryos in one stimulated IVF cycle. Cost per live birth was lower in the tubal surgery group (SGD27,109 vs SGD52,438). One hundred patients participated in the survey. A majority of patients preferred tubal surgery to IVF (68.2% vs 31.8%) before given information on the procedures, but indicated a preference for IVF (54.6%) to surgery (45.4%) after receiving information on the procedures. CONCLUSIONS: For women less than 40 years of age, desiring fertility after tubal ligation, laparoscopic tubal re-anastomosis offers better live birth rates and cost-effectiveness. Patients in Singapore are equivocal as to their preference after education regarding the choices. Thus, laparoscopic tubal re-anastomosis remains a viable alternative to IVF treatment.

GnRH agonist trigger and ovarian hyperstimulation syndrome: relook at 'freeze-all strategy'.

A case is reported of early onset ovarian hyperstimulation syndrome (OHSS) after gonadotrophin-releasing hormone agonist (GnRHa) trigger for final oocyte maturation in a GnRH antagonist protocol. The use of GnRHa in place of HCG as a trigger for final oocyte maturation in an antagonist IVF cycle has been proposed as a method for preventing OHSS in predicted high-responders. This approach, however, did not prevent the occurrence of OHSS in our case despite a freeze-all strategy. To the best of our knowledge, this is a possible index case of severe OHSS with GnRHa trigger for oocyte maturation without any luteal HCG rescue for a high responder, despite IVF cycle segmentation.

Adrenal tumours in pregnancy: diagnostic challenge and management dilemma.

Adrenal gland tumours in pregnancy are very rare occurrences and have highly variable clinical presentations. The timely diagnosis of adrenal tumours in pregnancy is extremely important, as failure to do so may lead to fatality. As there is limited published literature on adrenal tumours in pregnancy and no consensus on its management, the management of such patients with regard to medical and surgical treatments, as well as timing of delivery, must therefore be individualised and carried out with multidisciplinary expertise. We present two cases of adrenal tumours in pregnancy, both with favourable outcomes and variable gestations. Our first and second cases discuss a large phaeochromocytoma and a cortisol-secreting adrenal cortical adenoma in pregnancy, respectively.