Gametogenesis & Menstrual Cycle, Dysmenorrhea

Gametogenesis

Spermatogenesis

• Begins at: Puberty.

• Occurs in: Seminiferous tubules.

• Size of sperms: 50–60 microns.

• Fertilizable span: 48–72 hours.

• Time to form spermatogenesis: 70–75 days (72 days).

• Sperms attain maturity in: Proximal end of epididymis.

• Sperms attain motility in: Distal end of epididymis.

• Time for sperm maturation: 12–14 days.

• Total time to form mature sperm: 90 days (74 + 14 days).

Oogenesis

• Begins: Intrauterine.

• Fertilizable span of ova: 12–24 hours.

• Size of mature follicle: 18–20 mm (Graafian Follicle).

• Number of follicles:
• Maximum: 6–7 million at 5th month of intrauterine life (20 weeks of pregnancy).
• At birth: 1–2 million.
• Puberty: 4–5 lakh.

• Follicles undergo apoptosis.

Menstrual Cycle

• More cycles in a year
• Polymenorrhea

• Less cycles in a year
• Oligomenorrhea
• Interval >38 days apart

First Half of Cycle

• Also called: Proliferative/Follicular phase

• Main hormone: Estrogen.

• Ovarian cycle initiated by: FSH.

Hormones formed by ovarian granulosa cells:

• Estrogen (E2) (during follicular phase)

• Inhibin B.

• AMH (Small antral & pre-antral follicles).
• Glycoprotein hormone
• Gene for MIS/AMH
• Chromosome 19
• Produced by
• Sertoli cells at 7 weeks
• Granulosa cells of preantral and small antral follicles
• Function: Regression of Mullerian Duct in males.
• Best test for Ovarian reserve
• Done any day
• 1 - 3 = Normal
• High AMH
• > 3: PCOS
• > 3.3: High risk of OHSS
• Good outcome of IVF
• Low AMH
• <1 = Suggestive of POI (Poor Ovarian reserve)
• <0.5 = Diagnostic of POI

Applied aspect

• Tumor marker for granulosa cells
• Inhibin
• AMH (New marker)

• Granulosa tumor → feminising tumor

• Estrogen effect on FSH:
• Negative.

• Estrogen effect on LH:
• Negative
• Positive: when >200 pg for 48 hrs → LH Surge.

• Inhibin effect on FSH:
• Negative.

LH Surge

• Initiated by: Estrogen (>200 pg for 48 hrs).

• Maintained by: Estrogen + progesterone.

• Before ovulation: Both LH & FSH surge.

• Ovulation due to: LH surge.
• LH acts on Theca cells to produce Androgens.
• Androgens convert to Estrogen (E2).

• In granulosa cells: Androgens convert to Estrogen(E2).

• In adipose tissue: Androgens convert to E1

Ovulation

• Primary oocyte differentiates to Secondary oocyte/egg.

• Follicle forms Corpus luteum.

Time Between Peaks

• LH surge and ovulation: 32–36 hours (Best), 24–36 hours.

• LH peak and ovulation: 10–12 hours.

• Estrogen peak and LH peak: 12–24 hours.

Second Half of Cycle

• Also called: Secretory/Luteal phase.

• Main hormone: Progesterone.

Progesterone

• In low concentration: +ve on LH, FSH.

• In high concentration: -ve on LH, FSH.

• Duration of luteal phase fixed to: 14 days.

Corpus Luteum

• In non-pregnant females:
• Maintained by LH.
• Life span 12–16 days.

• In pregnant females: Maintained by hCG.

• Hormone which prevents luteolysis: hCG.

• Maximum size and activity seen on: 8 days after ovulation (D-22).

• Maximum progesterone seen on: D-22.

• Minimum LH & FSH seen on: D-22.

• All tests for ovulation done on: D-22 = 1 week before menstruation.

• Day of ovulation: 14 days prior to next menstruation (Length of cycle – 14 days).

• Pain at time of ovulation (mid-cycle abdominal pain):
• mittelschmerz syndrome.

NOTE

NOTE

Associations of Estrogen Dependent Conditions

Estrogen Dependent Conditions

1. Fibroid

2. Endometriosis

3. Endometrial Carcinoma

4. Ovarian Carcinoma

Common Risk Factors

• Nulliparity

• Obesity

• Early menarche

• Late menopause

Protective Factors

• Multiparity

• Pregnancy

• Physical exercise

• Smoking
• Due to aromatase inhibition

Incessant Ovulation Theory

• Definition:
• Increased ovulation → Leads to increased risk of ovarian carcinoma

• Variable risk
• PCOS
• Ovulation inducing drugs

• Protective factors:
• OCP (Oral Contraceptive Pills)
• Breastfeeding

Key Clinical Notes

• Virilizing ovarian tumor: Arrhenoblastoma

• Most common post-menopausal bleeding
• M/C cause in India: Cervical cancer.
• M/C cause:
• Polyp (37%)
• Deepthi Bahl → Still Endometrial Atrophy > Plyp
• 2nd M/C cause: Endometrial atrophy/Senile endometriosis (30%).

Dysmenorrhea

Pain at Time of Menstruation

Primary/Spasmodic Dysmenorrhea

• Pathology: Progesterone (relaxant) withdrawal causes vasoconstriction → Release of PGF2α → leading to pain (No pelvic pathology).

• Presentation: 
• Young female
• c/o pain since menarche except initial few cycles
• Anovulatory

• Pain Location: Suprapubic area (Generalized).

• Pain Character: 
• Just before or at menstruation;
• relieved within 72 hours.

• Pain Progression: 
• Pain decreases on its own;
• After physical act;
• Marriage;
• Child birth.

• P/V: Normal.

• Rx: NSAIDs or OCPs (makes the cycles anovulatory).

Secondary/Congestive Dysmenorrhea

• Causes: Pelvic pathologies.
• Endometriosis (m/c).
• Adenomyosis.
• Fibroid.
• Pelvic inflammatory disease.

• Presentation: 
• Reproductive age group female (33 years),
• C/o pain at the time of menstruation,
• Previously No h/o pain.

• Pain Location: Localized.

• Pain Character: Begins much before menstruation, and remains after menses.

• Pain Progression: Pain increases progressively.

• P/V: Abnormal.

• Rx: Manage the cause.