Fertility, Ectopic Pregnancy, and Ovarian Cancer Risk
It has been hypothesized that serous epithelial ovarian carcinoma, the most common and aggressive ovarian cancer subtype, arises primarily from the fallopian tube. As such, a history of fallopian tube dysfunction may be associated with an increased risk of ovarian cancer. Ectopic pregnancy, defined as a pregnancy that implants outside the uterine endometrium, occurs in 1-2% of all pregnancies and is one of the leading causes of maternal morbidity and mortality in the US and worldwide. Greater than 90% of ectopic pregnancies occur in the ampulla of the fallopian tube, and its risk factors include conditions that may confer fallopian tube dysfunction including endometriosis, pelvic inflammatory disease, Mullerian anomalies, and infertility. Thus, ectopic pregnancy and infertility, may be independent markers of ovarian cancer risk and women with these conditions may benefit from additional study and surveillance.
We hypothesize that a history of ectopic pregnancy confers an increased risk of ovarian cancer incidence and severity, and may be associated with a higher incidence of abnormal ovarian cancer screening parameters compared to those without a history of ectopic pregnancy. We propose to utilize existing data from the Prostate, Lung, Colorectal, and Ovarian (PLO) Cancer Screening Trial to examine the associations between ectopic pregnancy, fertility, and ovarian cancer.
Aim 1: To evaluate the incidence of ovarian cancer amongst women who have had an ectopic pregnancy and fertility-related factors which may modify risk
We hypothesize:
1) Prior ectopic pregnancy is associated with an increased risk of ovarian cancer
2) There is a reduction in ovarian cancer risk (interaction) in those that have a history of ectopic pregnancy and a prior live birth
3) There is an increase in ovarian cancer risk (interaction) in those with a history of ectopic pregnancy and endometriosis
Aim 2: To determine the association between a history of prior ectopic pregnancy, screening parameters, and severity of ovarian cancer at diagnosis
We hypothesize:
1) Those with prior ectopic pregnancy will have an increased incidence of abnormal ovarian cancer screening parameters (serum biomarker or ultrasound), and these screening parameters will be more likely to identify those with ovarian cancer
2) Prior ectopic pregnancy is associated with poorer prognosis at ovarian cancer diagnosis based on stage, grade, and/or histologic subtype
Aim 3: To determine the association between history of ectopic pregnancy and ovarian cancer mortality
We hypothesize:
1) Prior ectopic pregnancy is associated with a shorter time to ovarian cancer diagnosis
2) Prior ectopic pregnancy is associated with increased mortality from ovarian cancer
Aim 4: To evaluate the incidence of ovarian cancer amongst women with a history of infertility and how biomarkers and gynecologic history modifies that risk
We hypothesize:
1) Infertility is associated with an increased risk of ovarian cancer
2) There is a reduction in ovarian cancer risk (interaction) in those that have a history of infertility and a prior live birth
3) Ovarian cancer biomarkers will be differentially expressed in women with a history of infertility compared those without a history of infertility
Aim 5: To evaluate the association of a history of infertility with all-cause mortality, and specific causes of death
We hypothesize:
1) Infertility will be associated with a shorter lifespan compared to those without infertility
2) Infertility will be associated with an increased risk of death from cardiac, endocrine, and immune disorders
Natalie Stentz, MD, University of Pennsylvania
Kurt T. Barnhart, MD MSCE, University of Pennsylvania