Clinical Implications: Endocrine and the Placenta

Educational Objectives

The goal of this program is to improve management of pregnancy with regard to hormone function. After hearing and assimilating this program, the clinician will be better able to:

1. Illustrate the roles of various hormones during pregnancy.
2. Incorporate updated guidelines regarding prevention of preterm birth into practice.

Summary

Placenta: an endocrine organ capable of synthesizing most hormones and is responsible for the release of hormones into the fetal and maternal circulations; the placenta is composed of syncytiotrophoblasts and cytotrophoblasts; though both cell types produce peptide hormones, syncytiotrophoblasts primarily produce steroid hormones; the placenta lacks neural connections

Human chorionic gonadotropin (hCG): before implantation, hCG is produced by the cells of the forming embryo; after implantation, hCG is primarily produced by the syncytiotrophoblast layer of the chorionic villi and secreted into the intervillous space; hCG is the earliest biochemical marker of pregnancy and is detected in urine and blood 7 to 8 days before menses; hCG levels exponentially increase after implantation, doubling every 29 to 53 hr and increasing more slowly in abnormal pregnancies; an intrauterine pregnancy is expected to be seen with transvaginal ultrasonography when hCG measures ≈3510 mIU/mL (ie, discriminatory zone); hCG peaks at ≈100,000 mIU/mL at ≈10 wk gestation; higher-than-normal levels of hCG occur with multiple gestations, molar pregnancies, and in pregnancies with chromosomally abnormal fetuses

Corpus luteum: in early pregnancy, hCG helps preserve the corpus luteum, which produces progesterone (essential for maintenance of the early pregnancy); at 6 wk to 10 wk, a luteal placental shift occurs, after which point the placenta maintains the progesterone levels for the pregnancy; to prevent abortion (loss of the pregnancy), progesterone supplementation is necessary if the corpus luteum is removed before the placenta can maintain the progesterone level

Steroid Hormones

Progesterone: mainly synthesized from circulating maternal cholesterol and released into the maternal circulation; progesterone has anti-inflammatory and immunosuppressive functions to protect the fetus from immunologic rejection by the mother; progesterone is necessary for the maintenance of a quiescent (noncontractile) uterus and may help suppress the synthesis of prostaglandins (which induce labor or abortion); prevention of preterm birth (PTB) — PTB affects 1 in 8 deliveries and accounts for ≤85% of perinatal morbidity and mortality; Meis et al (2003) found that, compared with placebo, weekly 17 alpha-hydroxyprogesterone caproate (17-OHPC) injections significantly reduced the rate of recurrent PTB in patients with a prior spontaneous PTB (36.3% with 17-OHP vs 54.9% with placebo); in 2011, the United States Food and Drug Administration conditionally approved the use of 17-OHPC, and all patients with prior PTB were administered weekly intramuscular (IM) 17-OHPC 250 mg injections between 16 and 36 wk gestation; the PROLONG study (Blackwell et al [2020]) demonstrated no significant difference in the rate of PTB with use of 17-OHPC vs placebo; the American College of Obstetricians and Gynecologists does not recommend use of IM 17-OHPC in patients without history of PTB and cites insufficient data to support use of IM 17-OHPC for the primary prevention of PTB in patients with a prior spontaneous PTB; data are conflicting regarding use of vaginal progesterone in patients without a shortened cervix

Estrogen: estriol is the major estrogen hormone that is produced during pregnancy but more rapidly clears from circulation than estradiol, secondary to very low affinity for sex hormone-binding globulin; significantly high amounts of estrogen are produced during pregnancy; estrogen synthesis is primarily based on the interdependence of the fetus, the placenta, and the maternal compartment; the placenta is incapable of de novo estrogen production, but rather converts the dehydroepiandrosterone sulfate secreted by the fetal adrenal glands to estriol; data suggest that estrogen is not required for the maintenance of pregnancy, but can impact, eg, production of fetal lung surfactant, onset of parturition, lactation; placental steroid sulfatase deficiency (which causes X-linked ichthyosis) and placental aromatase deficiency (induces signs of virilization in mother and fetus) do not affect the maintenance of pregnancy

Peptide Hormones

Insulin-like growth factor (IGF): important for fetal growth; production of IGF may be partly regulated by placental growth hormones; fetal cord plasma levels of IGF positively correlate with birth weight and length of the fetus

Human chorionic somatomammotropin (HCS): possesses structural, biological, and immunologic similarities to pituitary human growth hormone and prolactin; HCS is thought to increase the supply of glucose to the fetus; HCS can help reduce insulin receptor sites and glucose transport in mothers with insulin sensitivity

Corticotropin-releasing hormone (CRH): synthesized by the placenta, chorion, amnion, and decidua; maternal serum levels progressively rise throughout pregnancy; as production of CRH-binding protein by the maternal liver decreases at term, it is thought that unbound CRH plays a role in the onset of labor; CRH concentration rapidly increases before labor but remains stable in patients undergoing planned cesarean delivery (who usually do not go into labor); CRH secreted into the fetal circulation may help drive the increase in cortisol production which helps with maturation of the fetal lungs and increased surfactant production

Oxytocin: may be administered to induce or augment labor; most patients receive oxytocin after delivery to decrease postpartum bleeding; placental oxytocin production is 5-fold greater than that of the posterior pituitary gland and is the main source during pregnancy; circulating levels of oxytocin are generally low throughout pregnancy, though oxytocin receptor concentration significantly increases just before onset of labor and during the second stage of labor to permit increased function

Readings

Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG study): a multicenter, international, randomized double-blind trial. Am J Perinatol. 2020;37(2):127-136. doi:10.1055/s-0039-3400227; Chatuphonprasert W, Jarukamjorn K, Ellinger I. Physiology and pathophysiology of steroid biosynthesis, transport and metabolism in the human placenta. Front Pharmacol. 2018;9:1027. doi:10.3389/fphar.2018.01027; Herrera CL, Maiti K, Smith R. Preterm birth and corticotrophin-releasing hormone as a placental clock. Endocrinology. 2022;164(2):bqac206. doi:10.1210/endocr/bqac206; Meis PJ, Klebanoff M, Thom E, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate [published correction appears in N Engl J Med. 2003 Sep 25;349(13):1299]. N Engl J Med. 2003;348(24):2379-2385. doi:10.1056/NEJMoa035140; Rauchfuss LK, Ainsworth AJ, Shenoy CC. Abnormal rate of human chorionic gonadotropin rise: a case series of patients with viable intrauterine pregnancies after embryo transfer. F S Rep. 2021;2(1):129-132. doi:10.1016/j.xfre.2020.11.006.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Gordon was recorded at USC Jorge H. Mestman Endocrine in Pregnancy and Women's Health Symposium 2024, held on February 24, 2024, in Los Angeles, CA, and presented by the Keck School of Medicine of the University of Southern California. For information on upcoming CME activities from this presenter, please visit https://keckusc.cloud-cme.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

OB711202

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.