Fertility: What can go wrong

• Low sperm count or quality• Failed ovulation• Failed fertilization• Failed or misplaced (ectopic pregnancy)

implantation• Malformed placenta• Miscarriage

Fertility: Why it goes wrong (1)• Hormonal imbalance

– Variation in hormone levels or hormone receptor levels– Environmental causes – Pituitary tumor or stress excessive prolactin levels – PCOS excessive LH levels (no LH surge)

• Anatomical problem/blockage– Innate low sperm quality or count (maybe also hormonal problem)– Testicular injury or surgery– Endometriosis – Inflammation or infection– Innate anatomical issue of reproductive tract

Fertility: Why it goes wrong (2) • Chromosomal abnormality

– No genetic info in egg (molar pregnancy)– Other abnormalities that cause spontaneous miscarriage

• Secondary to another condition/disease– Smoking or circulatory condition placental problems– Spinal cord injury fertility probably normal, but many risks

associated with delivery– Lupus flare up inflammation & drug treatment– Endometrial lining not thick enough, or lack of appropriate

receptors (does not receive correct hormonal signals)– Environmental toxins miscarriage – Menopause

DISCUSSION OF GNRH ARTICLE

WOMEN: Feedback loop of the early and midfollicular phases

• GnRH agonists: receptor desensitization by continuous administration (no pulsatile release)– Initial stimulation: “flare phenomenon”– Reduced FSH & LH after days-weeks

• GnRH antagonists: block GnRH receptors – React within hours

• Both result in greatly reduced release of FSH & LH, but timing is different

• GnRH receptors– Expressed in pituitary– Expressed in many tumors (even those not hormone-related)

• GnRH agonist effect on tumors– Antiproliferative– Antimetastatic– Antiangiogenic

• GnRH antagonist – Reduce LH and FSH release from pituitary – Behave like agonists on GnRH receptors in tumors (see effects

above)