Luteal Phase Defects and Progesterone Supplementation.

Importance: Luteal phase defects (LPDs), or an insufficiency of progesterone production during the luteal phase of the menstrual cycle, have been identified as a potential cause of recurrent pregnancy loss (RPL), but its exact contribution to RPL is not well-defined. In addition, the role of exogenous progesterone supplementation during pregnancy remains controversial. Objective: The goal of this review is to provide an updated, evidence-based summary of LPD, including prevalence and potential pathophysiologic mechanisms, and to explore the current controversies regarding progesterone supplementation for management and treatment of RPL. Evidence Acquisition: A literature review identified relevant research using a PubMed search, Cochrane summaries, review articles, textbook chapters, databases, and society guidelines. Results: Endogenous progesterone plays a crucial role in the first trimester of pregnancy, and therefore, insufficiency may contribute to RPL. However, the precise relationship between LPD and RPL remains unclear. Luteal phase defect is primarily a clinical diagnosis based on a luteal phase less than 10 days. Although there may be a possibility of incorporating a combined clinical and biochemical approach in defining LPD, the current lack of validated diagnostic criteria creates a challenge for its routine incorporation in the workup of infertility. Moreover, no treatment modality has demonstrated efficacy in improving fertility outcomes for LPD patients, including progesterone supplementation, whose inconsistent data do not sufficiently support its routine use, despite its minimal risk. It is imperative that women diagnosed with LPD should be worked up for other potential conditions that may contribute to a shortened luteal phase. Future work needs to focus on identifying a reproducible diagnostic test for LPD to guide treatment. Conclusions and Relevance: Currently, the perceived relationship between LPD and RPL is challenged by conflicting data. Therefore, patients with an abnormal luteal phase should undergo a thorough workup to address any other potential etiologies. Although supplemental progesterone is commonly utilized for treatment of LPD and RPL, inconsistent supporting data call for exogenous hormone therapy to be only used in a research setting or after a thorough discussion of its shortcomings.

Risk of neonatal and childhood morbidity among preterm infants exposed to marijuana.

BACKGROUND: Limited data exist regarding the neonatal and neurodevelopmental outcomes of infants exposed to marijuana (MJ) in-utero, particularly among preterm infants. We hypothesized that MJ-exposed preterm infants would have worse neonatal and childhood developmental outcomes compared to MJ-unexposed infants. METHODS: Secondary analysis of multicenter randomized-controlled trial of antenatal magnesium sulfate for the prevention of cerebral palsy was conducted. Singleton nonanomalous infants delivered <35 weeks exposed to MJ in-utero were compared to MJ-unexposed. Primary neonatal outcome was death, grade 3/4 intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and/or stage II/III necrotizing enterocolitis before discharge. Primary childhood outcome was death, moderate/severe cerebral palsy, or/and Bayley II Scales <70 at age 2. Backward-stepwise regression used to estimate odds of primary outcomes. RESULTS: 1867 infants met inclusion criteria; 135(7.2%) were MJ-exposed. There were no differences in neonatal (20% vs. 26%, p = 0.14) or childhood (26% vs. 21%, p = 0.21) outcomes in MJ-exposed infants compared to MJ-unexposed infants. In adjusted models, MJ-exposure was not associated with adverse neonatal outcomes (aOR 0.83 95% CI 0.47,1.44) or early childhood outcomes (aOR 1.47, 95% CI 0.97,2.23). CONCLUSIONS: Among infants born <35 weeks of gestation, MJ-exposure was not associated with adverse neonatal or childhood outcomes. Long-term follow-up studies are needed to assess later childhood neurodevelopmental outcomes following MJ-exposure.