1. Fertility: What can go wrong Low sperm count or quality Failed ovulation Failed fertilization Failed or misplaced (ectopic pregnancy) implantation Malformed placenta Miscarriage

2. 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

3. 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

4. DISCUSSION OF GNRH ARTICLE

5. WOMEN: Feedback loop of the early and mid follicular phases

6. 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

7. 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)