Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes.

Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures-a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE-each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery.

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.

Outcomes and cost analysis of single-embryo transfer versus double-embryo transfer.

BACKGROUND: Studies had compared single-embryo transfer to double-embryo transfer with cleavage stage embryos and found that while single-embryo transfer was less costly, it was also associated with a lower live birth rate than double-embryo transfer. A single blastocyst transfer has been shown to improve the live birth rate per cycle compared to single-embryo transfer at cleavage stage. OBJECTIVES: To compare live birth rates and real costs of elective single-embryo transfer to double-embryo transfer and to determine the incremental cost-effectiveness ratio of these two strategies in an unselected pool of women in a single center. DESIGN: Retrospective study. METHODS: We analyzed data of 4232 women who underwent their first fresh in vitro fertilization/intra-cytoplasmic sperm injection cycles with at least two embryos available for transfer in KK Women's and Children's Hospital from 2010 to 2017. RESULTS: Five hundred and sixty-four women underwent elective single-embryo transfer and 3668 women underwent double-embryo transfer. One hundred and fifty-six women who failed to achieve a live birth in their fresh elective single-embryo transfer cycle underwent a sequential thaw single-embryo transfer cycle. Live birth rate of fresh elective single-embryo transfer was significantly higher at 41.3% than that of double-embryo transfer at 32.6%. Cumulative live birth rate for sequential elective single-embryo transfer (fresh elective single-embryo transfer + thaw single-embryo transfer) was 47.9%. After accounting for variables which may affect live birth rates such as age and stage of embryo transfer, the odds of achieving a live birth from double-embryo transfer was 24% lower than that from sequential single-embryo transfer, although not statistically significant. For every live birth gained from an elective single-embryo transfer compared to double-embryo transfer, cost savings were S$20,172 per woman. If a woman had to have a sequential single-embryo transfer after a failed single-embryo transfer in her fresh cycle, cost savings were reduced to S$1476 per woman. CONCLUSION: Single-embryo transfer is a dominant strategy in an unselected population and adopting it in assisted reproductive treatments (ART) can produce cost savings without compromising on live birth rates.

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.

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.