Infertility Flashcards
Definition of Trends: Infertility
defined as the failure of a couple to conceive after 1 yr of unprotected intercourse
- if woman is over 35, it is a 6-month period of time
- trends & causes of infertility in Canada were poorly understood & defined until the late 90s , early 00s
- much of the info was based on conjecture & inference
- prevalence in Canada in 2001 was 8.5% (aprx. 250,000) infertile couples at that time
- due to paucity of the data before this century, difficult to comment on the trends of infertility, but there are a few misconceptions that the prevalence is increasing
- attributed to the though that couples are seeking out medical interventions for infertility sooner, possibly due to increased availability of treatments, meds, specialists , that the toal # of infertile couples have increased due to the baby boom era coming of reproductive age, ppl are talking more openly about their challenges in conceiving
Female Causes of Infertility?
Hormonal (ovulation disorders; PCOS where there is an excess of male hormones in the woman causing ovulatory issues, some imbalances that can cause recurrent miscarriage)
- endometriosis & PID can lead to fallopian tube occlusion
- Congenital anomalies in the female genital tract may also be an issue
- under modifiable risks (age- advanced maternal age impacts fetility)
- other factors can include weight & exercise
- for unexplained causes, research is focusing on connection between the immune & reproductive systems- females have a more reactive immune system than males for immediate infection protection but also increased female autoimmunity, development of antisperm antibodies both impacting fertility or pregnancy outcomes
Male factors for Infertility
- poor sperm quality, quantity, motility, shape, sexual dysfunction
- part of the workup of the infertile couple is to do a semen analysis (looks as shape, movement & number of sperm in a recently collected ejaculate sample after 3 days of abstinence)
- stressors, smoking, alcohol, tobacco & substance use & abuse may also affect either partner
What is Anovulation?
Breakdown in any one section of the feedback pathways can result in anovulation
- when a young woman achieves menarche it can take several yrs before the HPO axis is mature & ready to ovulate regularly
- in some cases irregular cycles persist due to alterations in the pathway
- this would be cycle lengths <24 days or >36 days
most women experience an occasional anovulatory cycle for reasons such as stress, weight changes or idiopathically
most common reason for anovulation is pregnancy
What is Amenorrhea?
Causes:
Normal ovarian hormone secretion:
- pregnancy, uterine dysfunction causes by (Hysterectomy, endometrial ablation or adhesions)
Decreases ovarian hormone secretion
– with high gonadotropin levels
-menopause, congenital ovarian failure caused by (Gonadal dysgenesis, resistance to gonadotropins) acquired ovarian failure caused by ( autoimmune disease, chemotherapy, resistance to gonadotropins, environmental toxins) premature ovarian failure
–with low gonadotropin levels
- secondary ovarian failure caused by ( hypothalamic-pituitary disorders eg. tumor, head trauma), functional hypothalamic-anovulation eg. starvation, psychogenic disturbance, hypothyroidism)
–with low or normal gonadotropin levels
- excessive testosterone, PCOS, excessive DHEAS, adrenal tumors, excessive progesterone, congenital adrenal hyperplasia
Increased ovarian hormone secretion
- ovarian dysfunction caused by feminizing tumors, masculinizing tumors, PCOS.
What occurs due to increased levels of prolactin?
hormone required for lactation, can suppress the appropriate response of the pituitary gland
- these elevated hormone levels can eb due to a prolactinoma (tumor of pituitary)
- chronic starvation such as in anorexia, can result in this
Thyroid gland alteration effects?
changes in mestrual cycle length, blood flkow
- which can lead to oligomenorrhea (cycles longer than 36 days), and potential ovarian failure
- hypothyroidism can interfere with normal GnRH secretoin which is needed for follicular development & ovulation
- decrease in release of LH can lead to wife range of menstrual dysfunction & the gonadal dysfunction of FSH/LH may decrease the amount of thyroid hormone availability for the necessary ovarian function
- thyroid hormone receptors have been found on the oocytes & surrounding granulosa cells
- both the hCG & maternal thyroxine are required to achieve fertilization, blastocyst development & fetal brain development
- multifactorial, hypothyroidism doesn’t always lead to infertility
Ovarian cyst effects on infertility?
impact ovulation as they send altered feedback signals to the HPO axis that may result in irregularities in the cycle
- PCO (polycystic ovary or ovarian syndrome) is an extreme form of a cystic overy that resut in chronic anovulation, endometrial hyperplasia, and other pathologic conditions
What is PCOS (Polycystic Ovary Syndrome)?
“string of pearls” appearance on Ultrasound
- volume of ovary can be enlarged, normal ovarian volume is <9 ml
- common endocrine disorder, associated with primarily hyperandrogenemia +/- anovulation & its associated infertility & with the clinical manifestations of oligomenorrhea (less freq. menses), hirsutism (excess hair growth which can occur in a more male pattern distribution) and acne
- exact prevalance is unknown, felt that with increased obesity rates = higher rates of PCOS as there is a link
- exact etiology unknown, genetic basis is suspected
Follicles in the Ovaries: PCOS?
key defining & morphological feature of this syndrome is the increased # of follicles as compared to a normal ovary
- increased follicles over produce androgens= androgenemia
Criteria to differentiate a normal from PCOS ovary:
- increase volume >9mls
- 10 or more follicles of 2-18mm diameter
- increase in amount & density of the ovarian stroma
- thickening of tunica
What is the Pathophysiology of PCOS?
associated with metabolic defect which presents as insulin resistance & hyperinsulinemia
- both muscle & adipose tissue demonstrate altered glucose uptake
- the gonadotropic effect of insulin on the ovarian tissue is unaffected & further increases the androgen production & premature cessation of follicular growth
- insulin reduces serum sex hormone-binding-globuline (SHBG)
- glycoprotein that binds testosterone & estradiol in circulation to make them inactive, there will be more active steroid available
Excess ovarian androgen production & less SHBG= increase in free testosterone & estrogen
- FSH is lower, elevated LH leads to androgens (DHEAS) levels from the adrenal cortex to be secreted in up to 50% of PCOS patients
blunted FSH/LH feedback leads to stimualtion for new follicles but not to full maturation or ovulation thus accounting for anovulatory cycles
= cyclic problem
Treatment for PCOS
to establish normal hormonal levels using oral birth control pill but for infertility
-sometimes Metformin is used to decrease the ovarian steroidogenesis
What happens to pregnant women with PCOS?
increased risk of GDM, G-HTN, preterm birth & perinatal mortality
Potential later consequences of PCOS?
dyslipidemia, Cardiovascular disease, DM, or metabolic syndrome
What is the effect of Late Maternal Age?
age results in declining quality of the ova as they have continued to be exposed to potential lifestyle choices of alcohol, tobacco, and poor diet
- achieving pregnancy becomes more difficult
- if woman does achieve pregnancy, there is higher spontaneous miscarriage rate that may also impact her ability to carry fwetus to term
- risk of G-HTN & GB increases
Fertility declines after age 35 for most women & this is multifactorial
