Pathophysiology, treatment and prevention of ovarian hyperstimulation syndrome.

PURPOSE OF REVIEW: Severe ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that affects 1% of women that undergo treatment with assisted reproductive technology. The review aims to summarize recent evidence on pathophysiology, treatment, and prevention of OHSS. RECENT FINDINGS: The pathophysiology is still not completely understood; however, vascular endothelial growth factor is likely to be an important mediator. Human chorionic gonadotropin was previously thought to be necessary for OHSS to occur; however, recent case reports have proven otherwise. The contribution of an attenuated anti-Mullerian hormone signalling pathway and CD11c + HLA-DR + dendritic cells and associated interleukins has been explored recently as contributors to pathogenesis.Treatment is largely supportive and is based mainly on consensus statements rather than evidence. Therefore, it is important to prevent this condition by identifying women at risk, allowing the clinician to implement preventive strategies, including the use of GnRH antagonist cycles with agonist triggers. SUMMARY: More research is required to elucidate the pathophysiology behind the condition. Clinicians should employ strategies to prevent OHSS.

RANZCOG CREI Consensus Statement on treatment of Ovarian Hyperstimulation Syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an uncommon but important iatrogenic condition associated with considerable morbidity and a small risk of mortality. This document gathers the consensus of a group of fertility subspecialists to aid health professionals in the development of protocols and guidelines for the management of women with OHSS. AIM: To produce evidence-based consensus statements on the treatment of ovarian hyperstimulation syndrome (OHSS). METHODS: The CREI Consensus Group met in 2013 and 2014 and identified issues for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted. RESULTS: There is a paucity of good data regarding the treatment of this condition, and much of the treatment is supportive in nature. Most of the management recommendations are based on good clinical practice points, rather than evidence from randomised trials. CONCLUSION: OHSS is an uncommon but serious condition for which there are a number of proven preventative strategies. Once OHSS is present, the treatment of OHSS is mainly supportive, and more research is required to elucidate treatment options targeted specifically at the main causative factors, to better treat the condition.

Elevated progesterone in GnRH agonist down regulated in vitro fertilisation (IVFICSI) cycles reduces live birth rates but not embryo quality.

OBJECTIVE: To assess the impact of pre-hCG elevated progesterone on live birth outcomes during GnRH agonist long down regulated protocol assisted reproduction cycles. DESIGN: Retrospective cohort study. SETTING: Single Centre Private IVF Clinic. PATIENTS: A total of 582 consecutive cycles of IVF/ICSI in 2003. INTERVENTIONS: All patients underwent a long down-regulation protocol, controlled ovarian stimulation and IVF/ICSI. Serum progesterone concentrations were measured just prior to HCG administration. 253 patients were followed to 2009 for outcomes of their frozen embryo cycles. MAIN OUTCOME MEASURE: Live birth rate in fresh and frozen cycles. RESULTS: Patients in the upper quartile pre-hCG progesterone concentration (≥ 5.4 pmol/L) had a higher final estradiol level, more oocytes collected and more usable embryos, when compared to those with lower quartiles. They also had lower live birth rates per cycle started (21.9% vs. 15%, P < 0.05). However, live birth rates from frozen embryo cycles were not significantly different between the groups. CONCLUSIONS: Pre-hCG progesterone elevation leads to lower live birth rates in stimulated IVF cycles. Live birth rates achieved with frozen embryos in the high progesterone cycles suggest, that pre-hCG progesterone elevation negatively affects endometrial receptivity without adversely affecting embryo quality.

Luteal phase defect: part of the infertility zeitgeist or relic from the past?

Luteal phase defect (LPD) or short luteal phase is a controversial entity that has been variously defined over the years. There are a number of potential causes for LPD all of which are associated with inadequate progesterone secretion throughout the luteal phase which impairs endometrial development and is thus thought to cause infertility. However, the relationship between LPD and infertility is complex, with LPD found in both fertile and infertile women. Attempts have been made at treating LPD with a number of regimens including progesterone supplementation and ovulation induction using clomiphene citrate, however, problems with study design have prevented conclusive evidence for the efficacy of these treatments being drawn. Practically, with the more interventionalist and aggressive approaches to managing couples with unexplained infertility, LPD may have become an irrelevant entity.

Atypical presentation of intramedullary spinal cord lesion.

We report a patient who presented with atypical clinical manifestations including worsening abdominal pain from an intramedullary spinal cord lesion. It is important to consider non-abdominal causes of abdominal pain for patients with an atypical presentation. The described case demonstrates the challenges facing the physician with the early diagnosis of acute abdominal pain. Spinal cord lesions, although uncommon, remain a potentially disabling and life-threatening cause of abdominal pain.

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome.

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.