EAST 501 Lecture Notes - Lecture 6: Ovarian Cancer, Assisted Reproductive Technology, Combined Oral Contraceptive Pill
21 Jun 2018
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Jan 22nd – Lec 6 Bernard
Presentation 1: Is IVF Safe?
1
OUTLINE:
1. Potential Risks for the mother
a. Breast Cancer
b. Ovarian Cancer
2. Potential Risks for the offspring
a. Physical/Developmental Disorders
i. Neurological Disorders/Mental Disorders
ii. Congenital Heart Disease
b. Genetics Disorders
i. Y Deletions
ii. Congenital Bilateral Absence Vas Deferens
c. Epigenetic Disorders (genomic imprinting)
i. Mechanisms
ii. Evidence
WHY WOULD WE EXPECT AN INCREASE IN THE INCIDENCE OF BREAST CANCER WITH IVF TREATMENTS?
- Fertility treatments are associated with an increase in endogenous E2 and exogenous P levels
- Prolonged exposure to these hormones have been linked to hormone receptor positive breast cancers
o Hormone replacement therapy (menopause), combination oral contraceptives
- with IVF, before they collect the eggs the E2 is extremely high compared to normal à in this process more
follicles are developing and producing E2 and the E2 can act on E2 receptors in the mammillary tissue in the
breasts à proliferation
A SIGNIFICANT INCREASE IN BREAST CANCER (BC) RISK AMONG IVF WOMEN WITH RESPECT TO WOMEN WHO GAVE
BIRTH NATURALLY
- women who were infertile and gave birth through IVF were more likely to develop BC
- Hazard ratio (HR) with 95% CI of breast cancer in ART women vs. controls
- HR of ~1.2 in those having undergone ART compared to the controls
- Study:
o Strengths:
§ large population (n=808,834)
§ data is controlled for cancer that developed prior to the study
§ adjustments made for age and parity (can influence the risks of developing BC)
§ excluded people who developed BC within one year of the IVF
o Limitations:
§ lack of data on family history, cause of infertility, lifestyle factors or previous contraceptive use
• these can all affect the risk of developing BC
§ lack of geographical variation
• just done in Norway à did not take into account variability in ethnicity or environment
§ weak control group
• control group: both IVF usage and infertility were variables
NO SIGNIFICANT INCREASE IN BREAST CANCER RISK AMONG IVF WOMEN WITH RESPECT TO NON-IVF INFERFILE
WOMEN
- compared women who were infertile and went through IVF compared to women who are infertility and did not
use any fertility treatment
- no increase in the incidence of developing BC à there was actually a slight decrease in the risk
- the only result that was statistically significant was in using progestin as a fertility drug
Jan 22nd – Lec 6 Bernard
Presentation 1: Is IVF Safe?
2
- for breast cancer:
o no fertility treatment HR = 1.00
o any fertility treatment HR = 0.87
o IVF HR = 0.9
- Strengths:
o large population (n=87,403)
o adjustments made for lifestyle factors (weight, smoking, drinking), age, parity
o data on drug therapy and cause of fertility is present (unlike first study)
o strong control group à this shows that if there is a risk of using IVF it is because of the IVF and not
because of other factors that influenced the results
- Limitations:
o lack of geographical variation (only in Israel à there could be genetic differences)
o lack of data on family history of cancer, oral contraceptive use
- based on the first two studies presented à there is no risk of developing BC in women who are infertile and
who have gone through IVF, but infertility itself increases the risk of having BC
WHY WOULD WE EXPECT AN INCREASE IN THE INCIDENCE OF OVARIAN CANCER WITH IVF TREATMENTS?
1. Gonadotropin therapy may promote malignant changes by stimulating the surface epithelium of the ovaries,
initiating cancer development
a. increased expression of Chorionic Gonadotropin beta polypeptide 5 (CGB5) subunit of hCG promotes
angiogenesis in OVCAR3 cells, supporting tumor growth within the ovary
§ there was a study done in mice where they used a viral vector to transfect ovarian cells into
mice (came from a human cell line)
§ they found that with the expression of a CGB5 it promoted angiogenesis in the cells and
angiogenesis promotes tumors growth à promoted cancer
2. Each event of ovulation promotes DNA damage and replication errors within the ovarian surface epithelium
a. stimulating ovulation will lead to increased rates of DNA damage in the ovaries
DECREASED RATES OF OVARIAN CANCER IN MUTANT-RESTRICTED OVULATOR HENS
- chickens ovulate a lot more than humans
o in a period of 3 years à ~400 times (in humans it is 6 times)
- they genetically modified the hens to make some of them into restrictive ovulators
o they ovulated a few times (or none)
- the incidence of cancer diagnoses was the highest in the hens that ovulated the most times
- by restricting the ovulation, it decreased the incidence of ovarian cancer by 9x
NO SIGNIFICANT INCREASE IN THE RISK OF OVARIAN CANCER WITH RESPECT TO THE INFERTILE POPULATION
- this was a meta-analysis that pooled data from 9 cohort studies
- compared infertile women who went through IVF to the general population and women who were infertile and
did not receive treatment
o compared to the general population there was a statistically significant increase in the risk of developing
ovarian cancer à but most of the people in the “general population” group are fertile (important to
note)
o compared to the infertile women who did NOT receive IVF there was not a statistically significant
increase in the risk of developing ovarian cancer
- general population Effect estimate = 1.65
infertile women Effect estimate = 1.05
Document Summary
Outline: potential risks for the mother, breast cancer, ovarian cancer, potential risks for the offspring, physical/developmental disorders, neurological disorders/mental disorders, congenital heart disease, genetics disorders, y deletions, congenital bilateral absence vas deferens, epigenetic disorders (genomic imprinting, mechanisms, evidence. Fertility treatments are associated with an increase in endogenous e2 and exogenous p levels. Prolonged exposure to these hormones have been linked to hormone receptor positive breast cancers: hormone replacement therapy (menopause), combination oral contraceptives. A significant increase in breast cancer (bc) risk among ivf women with respect to women who gave. Women who were infertile and gave birth through ivf were more likely to develop bc. Hazard ratio (hr) with 95% ci of breast cancer in art women vs. controls. Hr of ~1. 2 in those having undergone art compared to the controls. Data is controlled for cancer that developed prior to the study. Adjustments made for age and parity (can influence the risks of developing bc)
