Anti-Mullerian hormone changes in pregnancy

ii To my family and friends who supported me throughout this journey iii ACKNOWLEDGMENTS This project would not have been possible without Drs. Donna and Mark Santillan. I would like to thank them both for their endless support and advice in the development of this program. Thanks to Dr. Kristi Borowski for allowing us access to her serum tissue bank and birth certificate data, and to Dr. Ben Leader at Reprosource for his assistance with the AMH samples. your valuable input, and your endless flexibility with my schedule that allowed me to complete this thesis despite the challenges of my work environment. And finally, I would like to thank Dr. Elaine Smith for her friendship and endless mentoring in in all things, including the art of fine wines. iv ABSTRACT When the delicate hormonal balance in early pregnancy is disrupted, the consequences can be significant. We have a poor understanding of the "cross-talk" in the fetal/placental/ovarian axis that is essential for normal fetal development. This lack of knowledge challenges our ability to recognize disruptions in this axis that may be a signal for future disease. As a result, our ability to apply preventive measures against adverse obstetric outcomes, such as preterm birth (PTB), are quite limited. Attempts to predict PTB using biomarkers of feto-placental health have been largely unsuccessful, but no one has considered the inclusion of ovarian biomarkers in these models. Anti-Mullerian hormone (AMH) is a biomarker of ovarian activity that has recently been found to decline in early pregnancy at a time that corresponds to the involution of the corpus luteum (CL). The signal for CL involution is believed to originate from the placenta; therefore, the AMH levels in pregnancy may reflect the degree of ovarian up or down-regulation based on feto-placental needs. As the major function of the CL in pregnancy is the production of progesterone, which acts as an anti-inflammatory agent in the placental bed, changes in CL-derived progesterone could result in higher or lower degrees of placental inflammation. Therefore, monitoring the changes in AMH levels may provide insight into the inflammatory state of the placenta which could be used as a signal for possible adverse obstetric outcomes resulting from a pro-inflammatory state, such as PTB. The first aim of this project was to test the hypothesis of an association between AMH levels in early pregnancy and PTB risk. When the differences in AMH levels between …