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Clinical Definition of Infertility
Inability to achieve pregnancy after 1 year of regular unprotected intercourse (or 6 months if female partner is >35 years old).
HPA-HPG Axis Stress Interaction
Psychological/physical stress activates the HPA axis; CRH downregulates hypothalamic GnRH secretion, suppressing LH/FSH and decreasing fertility.
SRY Gene Function
Located on the short arm of Y chromosome; encodes a transcription factor that suppresses DAX1, directing primordial gonads to differentiate into fetal testes.
Sex Determination Cascade (XY)
SRY represses DAX1 -> enables SOX9 and SF1 expression -> SOX9/SF1 bind AMH promoter -> Sertoli cells synthesize Anti-Müllerian Hormone (AMH).
Internal Sexual Differentiation (XY)
Sertoli cells secrete AMH (causes Müllerian duct regression); Leydig cells secrete Testosterone (maintains Wolffian ducts -> epididymis, vas deferens, seminal vesicles).
Internal Sexual Differentiation (XX)
Absence of SRY -> DAX1 active -> no AMH (Müllerian ducts develop -> Fallopian tubes, uterus, cervix, upper vagina); no Testosterone (Wolffian ducts degenerate).
5α-Reductase Function
Converts Testosterone into Dihydrotestosterone (DHT); DHT has a much higher binding affinity for the androgen receptor (AR) and drives male external genitalia development.
External Genitalia Homologies
Genital tubercle -> Glans penis (DHT) or Clitoris (no DHT); Labioscrotal swellings -> Scrotum (DHT) or Labia majora (no DHT); Urethral folds -> Penile shaft or Labia minora.
Complete Androgen Insensitivity (CAIS)
46,XY; SRY present, testes form & secrete AMH (no uterus) and T, but mutated AR prevents T/DHT action -> female external genitalia; T converted via aromatase at puberty -> breast development; primary amenorrhea.
5α-Reductase Deficiency (Guevedoces)
46,XY; SRY & testes present; Müllerian ducts regress and male internal ducts develop; lack 5α-reductase -> female/ambiguous external genitalia at birth; penis/scrotum develop at puberty due to high T spike. Congenital Adrenal Hyperplasia (CAH)
Turner Syndrome (45,X) & Klinefelter (47,XXY)
Turner: single X, streak ovaries, short stature, amenorrhea. Klinefelter: extra X with SRY, male structures, testicular atrophy, tall stature, low T.
Spermatogenesis Timeline & Yield
Begins at puberty in seminiferous tubules; 1 spermatogonium undergoes 2 meiotic divisions yielding 4 haploid spermatids (~42-76 days to mature).
LH & FSH Functions in Testes
LH stimulates Leydig cells to produce Testosterone; FSH stimulates Sertoli cells to produce Inhibin and Androgen-Binding Protein (ABP). Androgen-Binding Protein (ABP)
Sperm-Targeted Contraceptives
NES/T trial (progestin halts LH/FSH & sperm production; T maintains systemic traits); Nonoxynol-9 spermicide (degrades acrosome/motility); Copper IUD (Cu ions block motility & acrosomal enzymes); Vasectomy (cuts vas deferens).
Oogenesis Meiotic Arrest Stages
Primary oocytes arrested in Prophase I at birth; complete Meiosis I just prior to ovulation (extruding 1st polar body); arrest in Metaphase II until fertilization triggers completion (extruding 2nd polar body).
Two-Cell, Two-Gonadotropin Model
Thecal cells respond to LH by synthesizing androgens; Granulosa cells respond to FSH by using Aromatase to convert thecal androgens into Estrogens.
Mid-Cycle LH Surge Trigger
Sustained high levels of Estrogen (>200 pg/mL for >48 hr) from dominant follicle switch feedback from negative to POSITIVE feedback on pituitary; Ovulation occurs 16-24 hr post-LH surge.
Menstrual Cycle Phase Alignment
Ovarian Follicular Phase = Uterine Menstrual + Proliferative Phases (estrogen-driven); Ovarian Luteal Phase = Uterine Secretory Phase (progesterone-driven by corpus luteum).
Early Pregnancy & hCG Function
Trophoblast cells of blastocyst secrete human Chorionic Gonadotropin (hCG); hCG rescues corpus luteum to maintain progesterone and estrogen production for first 8 weeks, preventing menses.
Emergency Contraception Mechanisms
Levonorgestrel (Plan B) delays LH surge (<24-72 hr); Ulipristal acetate (Ella) progesterone receptor modulator effective up to 5 days, delays ovulation even after LH surge starts. Neither disrupts established implantation. Non-Contraceptive OCP Health Benefits
Gonadotropin Levels Across Life Span
Childhood: lowest levels, FSH > LH; Puberty & Adult: rising/pulsatile, LH > FSH; Senescence (Menopause/Andropause): highest lifetime levels due to loss of steroid negative feedback, FSH > LH.