FEMALE REPRODUCTION SYSTEM OOGENESIS DEVELOPMENT: 6-8 weeks GERMINAL EPITH. hormonally OOGONIA FOLLICLE independent mitotic division PRIMORDIAL 24 weeks OOCYTES I. 7 x 106 1. meiosis birth prophase 2 x 106 hormonally puberty OOCYTES II. 3 x 105 dependent haploid DOMINANT (cyclic) 2. meiosis ATRETIC metaphase GRAAF OVUM OVULATION 2. meiosis – end climacterical 0 Daan and Fauser, Maturitas 82 (2015) 257–265 UTERINE CYCLE ovarian uterine gonadoliberin (GnRH) FSH, LH estradiol basal temper. 0 4 14 28 MENS. PROLIPHER. SECRETORY PHASE + _ 0,5°C FOLICULLAR OV. LUTEAL PHASE 6-10x 2-3x progesteron Daan and Fauser, Maturitas 82 (2015) 257–265 OVARIAL CYCLE Germinal epithelium Primordial Primary Graaf Corpus haemorrhagicum C. luteum follicle 25m 150m up to 2 cm estradiol progesteron Oocyte-maturation inhibiting factor Vesicular follicle Luteinisation inhibiting factor (estrogens) (progestins) OVULATION methrorhagia VESICULAR FOLLICLE PRIMARY FOLLICLE - FSH Growth acceleration of primary follicle – change into vesicular follicle: 1) estrogens released into follicle stimulate granul. cells increased number of receptors for FSH – POSITIVE FEEDBACK (higher sensitivity for FSH!!!) 2) Increased number of receptors for LH (estrogens and FSH) – another acceleration of growth due to „higher sensitivity“ to LH 3) Increased estrogens and LH secretion accelerates growth of theca cells, secretion is increased explosive growth of follicle DOMINANT FOLLICLE 1. High level of estrogens from the fastest-growing follicle 2. Negative feedback on FSH production from adenohypophysis 3. Drop in FSH secretion 4. „Dominant follicle“ continues in growing due to intrinsic positive feedback 5. Other follicles grow slowly and subsequently become atretic MECHANISM OF OVULATION LH PROGESTERON Hyperaemia of follicle Secretion of prostaglandins Weakening of follicle wall PROTEOLYTIC ENZYMES (collagenases from theca externa) Degeneration of stigma Rupture of follicle Release of oocyte Transudation of plasma into follicle Swallowing of follicle HUMOURAL REGULATION OF CYCLE GnRH GnRH GnRH FSH LH FSH LH FSH LH Follicular phase Ovulation Luteal phase P FSH-rec. LH-rec. P P P A E A E A E A E 90´ 360´ GnRH FSH LH 30´ Artesia of follicle (except of one) Feedback -/+ Involution of corpus luteum EFFECTS OF OVARIAL HORMONES E P Ovaries: maturation of follicles Hysterosalpinx: motility motility Uterus: proteosynthesis proteosynthesis vascularisation and proliferation of endom. secretion of endom. glands motility glycogen motility Cervix: colliquation of „plug“ creation of „plug“ Vagina: cornification of epithelium proliferation of epithelium Mamma: growth of terminals growth of acines Secondary sexual signs + Adipose tissue: store (predilection), (critical amount) Bone tissue: absorption closure of fissures development of pelvis Total water retention: + + Sexual behaviour: + - ASSISTED REPRODUCTION TECHNIQUES 1. STIMULATION OF OOGENESIS (maturation of more follicles) 2. STIMULATION OF SPERMIOGENESIS (vit. E) 3. INSEMINATION (treated sperm, applied deeply into uterus) 4. IVF (in vitro fertilisation) Ad 1) PROTOCOLS OF OVARIAL STIMULATION (short of long stimulation protocols) Stimulation of ovaries –FSH and LH, 3. - 12. day of cycle, SOMETIMES combined with GnRH agonists or antagonists IVF PROCEDURES 1. STIMULATION OF OVARIES 2. TIMING OF TAKING THE OOCYTES 3. EXTRACORPOREAL FERTILISATION OF OOCYTES 4. EMBRYOTRANSFER AND MAINTAINANCE THERAPY Ad 2) TIMING OF TAKING THE OOCYTES Between 12. and 17. days of cycle, US controlled, after stimulation of oocyte maturation by hCG, aspiration from follicular liquid in analgesia or anaesthesia Ad 3) EXTRACORPOREAL FERTILISATION OF OOCYTES (cultivation of sperm and oocytes in vitro for 48 hrs; test of sperm surviving – min.40%; micromanipulation techniques – ICSI a AH = gentle rupture of zona pellucida; prolonged cultivation – up to 120 hrs) Ad ) EMBRYOTRANSFER (transfer of max. 3 embryos in stage of morula or blastula; genetic examinations) and MAINTENANCE THERAPY (progesterone) CONTRACEPTION (BIRTH CONTROL) • RHYTHM METHOD • SPERMICIDE SUBSTANCES • COITUS INTERRUPTUS • CONDOM, PESSARY • IUD • HORMONAL CONTRACEPTIVES – risk of failure less than 1% • VASECTOMY AND LIGATION OF HYSTEROSALPINX Hormonal curettage (excochleation). Substitution therapy in climacterium. HORMONAL CONTRACEPTION • block of ovulation by suppression of hypothalamic releasing hormones (block of preovulatory surge of LH) • changes of character of cervical plug (progestin thickens mucus) • changes of endometrium (suppression of its growth) • changes of hysterosalpinx motility Combined hormonal contraceptives: • monophasic (amount of oestrogen and gestagen is stabile) • biphasic and triphasic • combiphasic contraceptives (after 7 days gestagen content increases and oestrogen content decreases) 15mg estrogenu 60mg progestinu