patho: infertility

what is infertility

• Infertility = failure of a couple to conceive after 1 year of unprotected intercourse

what is the time period determining infertility for woman over 35

6 months

what were trends for infertility in 2001

•  8.5% using 1-year definition
  → ≈ 250,000 infertile couples

• Limited data before this century → difficult to comment on trends

• Misconception that prevalence is increasing

what were possible reasons for misconceptions for inferitlity

• Couples seeking medical intervention sooner → increased availability of treatments, medications + specialists

• Baby boom era reaching reproductive age

• People talking more openly about challenges conceiving

• US: rate = 10.2%, shown not to have changed from 1965 data → present

what percentage of population causes infertility

• Female: ~40%

• Male: 30–40%

• Unknown: 10–20%

• Small % = couple issue

  • Neither person alone has an issue, but together there is a problem

what hormonal factors in females cause infertility

• Ovulation disorders

• PCOS → excess male hormones → ovulatory issues

• Some hormonal imbalances → recurrent miscarriage

• Endometriosis + PID → fallopian tube occlusion

• Congenital anomalies of female genital tract

what are modifiable risks for women

• Age / advanced maternal age

• Weight

• Exercise

what hormonal factors in males cause infertility

• Poor sperm:

  • Quality

  • Quantity

  • Motility

  • Shape

• Sexual dysfunction

what is looked at for semen analysis

• Looks at sperm shape, movement + number

• Recently collected ejaculate

• After 3 days abstinence

what are other issues that may cause infertility

• Stressors, smoking, alcohol, tobacco + substance use/abuse → may affect either partner

• Newer research → connection between immune + reproductive systems

  • Females have a more reactive immune system → immediate infection protection

  • Can also lead to increased female autoimmunity

  • Development of antisperm antibodies → may impact fertility and/or pregnancy outcomes

what is anovulation

breakdown anywhere in feedback pathways of ovulation

what timeline constitues an irregular cycle

• Irregular = cycle <24 days or >36 days

what causes irregular cycles

• Stress

• Weight changes

• Idiopathic causes

what is the most common reason for anovulation

• pregnancy

what is amenorrhea

absense of menstrual period

how can we evaluate amenorrhea

stepwise approach to diagnostic tests/procedures

• Divide possible disorders based on:

  • Ovarian hormone secretion profile

  • Then gonadotropin levels

what ovarion hormone profiles can evaluate amenorrhea

• Normal ovarian hormone secretion
  → think uterine function

  • Is a uterus present?

  • Has surgery affected ability of uterus to permit implantation?

  • Pregnancy → loss of menses with normally functioning ovaries

• Increased ovarian hormone secretion
  → think why there is increased secretion

  • Are ovaries enlarged due to tumours?

• Decreased ovarian hormone secretion
  → look higher in HPO axis at hypothalamic-derived gonadotropins

what gonadotropin profiles can evaluate amenorrhea

• High gonadotropins
  → hypothalamus working very hard to get ovaries to respond

  • Menopause

  • Ovarian failure

  • Previous chemotherapy affecting ovaries

• Low/normal gonadotropins
  → consider other hormones impacting system

  • Adrenals

  • Other steroid hormones

• Low gonadotropins
  → think higher structures:

  • Hypothalamus

  • Pituitary glands

• ↑ Prolactin

  • Required for lactation

  • Can suppress appropriate pituitary response

  • Causes:

    • Prolactinoma = pituitary tumour

    • Chronic starvation, e.g. anorexia

what does an alteration in thyroid function lead to

menstural cycle changes

• Cycle length

• Blood flow

• Potential ovarian failure

• oligomenorrhea

• Hypothyroidism → interferes with normal GnRH secretion

  • GnRH essential for follicular development + ovulation

• ↓ LH release → wide range of menstrual dysfunctions

• Gonadal FSH/LH dysfunction → may ↓ thyroid hormone availability needed for ovarian function

what is oligomenorrhea

cycles >36 days

what effect does hypothyroidism have on menorrhea

• Hypothyroidism → interferes with normal GnRH secretion

  • GnRH essential for follicular development + ovulation

• ↓ LH release → wide range of menstrual dysfunctions

• Gonadal FSH/LH dysfunction → may ↓ thyroid hormone availability needed for ovarian function

where are thyroid receptors found

• Oocytes

• Surrounding granulosa cells

Both hCG + maternal thyroxine seem required for

• Fertilization

• Blastocyst development

• Fetal brain development

what effects do ovarian cysts have on amenorrhea

altered feedback signals to HPO axis → may impact ovulation + cause cycle irregularities

what is PCOS/PMOS

PCOS = common endocrine disorder in women

what primarly causes pcos

• Hyperandrogenemia ± anovulation

• Associated infertility

what are clinical manifestions of pcos

• Oligomenorrhea = less frequent menses

• Hirsutism = excess hair growth, possibly male-pattern distribution

• Acne

what is the prevalence and etiology of pcos

• Exact prevalence unknown

  • Increasing obesity rates may → higher PCOS rates; seem linked

• Exact etiology unknown

  • Genetic basis suspected

  • Understanding improving through research

what is pcos from a reproductive viewpoint

• Look at follicles in ovaries

• Increased follicles → overproduce androgens → androgenemia

what are key defining/morphological features of pcos

increased number of follicles compared with normal ovary

what is the metabolic defect of pcos

• Insulin resistance + hyperinsulinemia

• Altered glucose uptake in muscle + adipose tissue

what is the gonadotropic defect of pcos

•  effect of insulin on ovarian tissue remains unaffected
  → ↑ androgen production
  → premature cessation of follicular growth

what occurs to insulin serum in pcos

• Insulin ↓ serum SHBG

what is SHBG

• SHBG = glycoprotein that binds testosterone + estradiol → makes them inactive

• ↓ SHBG → more biologically active steroids

what causes androgen production + less SHBGA

→ ↑ free testosterone + estrogen

what occurs to FSH snd LH in pcos

• FSH typically lower

• ↑ LH → androgens, particularly DHEA-S from adrenal cortex

  • DHEA-S secreted in up to 50% of PCOS patients

• Blunted FSH/LH feedback
  → stimulation for new follicles
  → no full maturation/ovulation
  → anovulatory cycles

• “Very cyclic problem”

what are treatments for pcos

reestablishing normal hormone levels → oral birth control pill

what are treatments for infertility

• Metformin = oral antihyperglycemic, biguanide class

• Used to decrease ovarian steroidogenesis

what risks do pregnant women with pcos have

• GDM

• Gestational HTN

• Preterm birth

• Perinatal mortality

• Later sequelae:

  • Dyslipidemia

  • Cardiovascular disease

  • Diabetes mellitus

  • Metabolic syndrome

are women born with all oocytes/ova they will have in their lifetime

yes

what happens to ova with age

decline of quality

• Continued exposure to potential lifestyle choices: alcohol, tobacco, poor diet

what happens if pregnancy occurs during late maternal age

• ↑ spontaneous miscarriage rate

• May affect ability to carry fetus to term

• ↑ gestational HTN

• ↑ GDM

when does fertility decline for most women

after age 35

according to statisics canada when do most women experience first delivery

after age 30

what potential cost comes with donor eggs for older women

•  loss of genetic connection to child

what do untreated STIs do to women

•  blocked fallopian tubes
  → infertility + ↑ risk of ectopic pregnancy

what is a common cause of PID

Chlamydia + gonorrhea

what occurs to the lower pelvic tract form untreated STIs

ascending infection

Women often have no STI signs/symptoms due to site of infection what does this lead to

↑ number + severity of infections

what occurs from permanent fallopian tube injury

• Loss of cilia function

• Fibrosis

• Complete occlusion
  → ↓ chances of pregnancy

what should sexually active women do

advocate for themselves + request routine STI screening at annual exam

what effects does surgery have on infertiilty

• Surgery can alleviate blockages

  • Does not decrease ectopic risk

  • Not commonly done at this time

• Any abdominal/pelvic surgery → adhesions
  → fallopian tube constriction or poor ovum motility

• Endometriosis can also cause blockages

what ar Müllerian defects

embryological causes of infertility

what is HSG

evaluates patency of fallopian tubes

how does HSG occur

• Fluoroscopic examination → radiology department

• Speculum inserted into vagina

• Dye injected through small catheter into uterine cavity

• Clinician watches screen → dye should flow out of both tubes

what are surgical evaluation techniques of pelvis + uterus

• Hysteroscopy

• Diagnostic laparoscopy

• Dye transit

what colour is HSG dye

blue

→ checks for free spill from tubes into peritoneal cavity

is bilateral blockage common

no usually only one tube affected

what is endometriosis

Appearance of plaques of endometrial tissue on other structures

what other structures can have appearence of plaques

• Bowel

• Bladder

• Ovary

• Fallopian tube

• Other pelvic/peritoneal structures

how does endometriosis act

•  like endometrial tissue under monthly female hormones
  → swell + slough

• No egress/exit point unlike uterine os
  → can cause significant pain + scarring

  • Depends on location of implants

• Cause largely unknown

  • Some evidence supports retrograde menstruation

what questions are to be asked about endometriosis

• Is endometriosis a cause of infertility?

• Many women with children later found to have endometriosis

• Many women in infertility clinics also found to have endometriosis

• “Which came first? The chicken or the egg.”

• Did endometriosis cause infertility, or infertility cause endometriosis?

how is endometriosis initally diagnosed

clinical suspicion

what is a defintie diagnoses for endometriosis

laparoscopy

how do number of plaques versus location of plaques correlate to endometriosis

• Number of plaques often does not correlate with symptoms

• Location is more important:

  • Plaque on nerve root or ovary → may be more painful

  • Plaque on muscle mass → may be less painful

what is the mullerian system

Female genital tract

what occurs to mullerian system during embryogensis

• small changes in normal development can result in major anatomical anomalies at maturation

what happens if pregnancy is achieved + carries past viability with mullerian defects

• ↑ risk preterm delivery

• ↑ malpresentation at delivery:

  • Breech

  • Transverse lie

what are fibroid tumours

• Can exist on, in, or in muscle layers of uterus

• Alter shape of uterine cavity
  → preterm delivery or malpresentation

what are 3 types of treatments for infertility

• Medical

• Surgical

• Both

what is IUI

• Intrauterine Insemination (IUI) = least invasive

• Semen instilled directly into uterus

• May add ovarian stimulation

what is clomiphene

oral ovulatory agent

what is follitropin / gonal-F

•  injectable gonadotropin

  • Active ingredient = FSH

how do medications work for infertility

• Medications increase number of mature ova in a cycle
  → ↑ chances of pregnancy

what is IVF

• Ova + sperm combined outside body

• Develop for 3–5 days

• Resultant zygotes transferred into uterus

when is IVF used

• If IUI/ovarian stimulation fails → may proceed to IVF

how are ova collected for IVF

Ova collected by transvaginal aspiration of ovary under ultrasound guidance

what is done with excess zygotes in IVF

Excess zygotes may be frozen for future attempts

what can multiple zygote transfer cause

Multiple zygote transfer → risk of multiple gestation

what does risk of multiple gestation cause

• Multiple gestation → higher potential for maternal + fetal complications

  • Ethical debate about optimal number of transfers per cycle

• Current trend → fewer zygotes transferred
  → hopefully reduce risk of multiple gestations