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Role of AMH ScreeningDr Sujoy DasguptaMBBS (Gold Medalist, Hons), MS (OBGY- Gold Medalist), DNB, FIAOG
Fellow- Reproductive Endocrinology & Infertility (ACOG, USA)
Consultant, Bavishi Pratiksha Fertility Institute, Kolkata
Visiting Consultant, RSV Hospital, Kolkata
Secretary, Website and Bulletin Committee, Bengal Obstetric and Gynaecological Society (BOGS) 2017-18
Managing Committee Member, BOGS, 2017-18
Anti- Müllerian Hormone (AMH)
• Hormone found in the testes (Sertoli Cells)
• Müllerian regression and sexual differentiation in males
• 1986- Isolated from the Sertoli cells in the testes and the granulosa cells in the ovaries (Picard JY, et al.)
Physiology of Follicular Dynamics
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
FSH
70-80 daysLast 20 days
Initial Recruitment Cycle Recruitment Selection Dominance
Paracrine Control
(Gn Independent)
Endocrine Control
(Gn Dependent)
Estrogen
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
FSH
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
FSH
Estrogen
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
FSH
Initial Recruitment Cycle Recruitment Selection Dominance
Paracrine Control
(Gn Independent)
Endocrine Control
(Gn Dependent)
Estrogen
Primordial Follicle
Small Preantral
Large Preantral
Small Antral (2-7 mm)
Large Antral(8-12 mm)
Preovulatory
Atresia Atresia Atresia
1st
Migration
• Activin
• Inhibin
• TGF Superfamily
2nd
Migration
• GH
• IGF
• Androgen
AMH
FSH
70-80 daysLast 20 days
Initial Recruitment Cycle Recruitment Selection Dominance
Paracrine Control
(Gn Independent)
Endocrine Control
(Gn Dependent)
Estrogen
Role of AMH in Ovarian Dynamics
• Follicular Preservation
• Prevention of unnecessary and excessive recruitment of primordial follicles
• Restriction of follicular sensitivity to FSH
• Indirectly helping mono-follicular development
Terminology1. Ovarian Reserve- Number and quality of oocytes present in the
ovary
2. Ovarian Responsiveness- Number of oocytes developed/ retrieved after COH
3. Ovarian Ageing- Decline in quantity and quality of ovarian activity because of individualized rhythm of the “biological clock”
Ovarian Reserve
When to screen for Ovarian Reserve
• Routine Tests in Sub-fertility (NICE 2013)
1. Semen Analysis
2. Tubal Patency- HSG, HyCoSy, Laparoscopy
3. Mid-luteal serum Progesterone
• Should AMH be included in routine investigation for Infertility?
NICE (2013)
For all types of Subfertility-
• Age
Before ART- Any one of
• AMH, FSH, AFC
Markers for Ovarian reserve
AMH- To screen for Ovarian Reserve
• Superior than other markers
• Paracrine control, independent of HPO endocrine feedback
• Correlates with AFC, FSH, Inhibin B, E2
• Higher sensitivity and specificity than conventional markers
• Remains relatively stable throughout the cycle (cf FSH, Inhibin B, E2)
• Low inter-cycle variability
Problem with AMH
• Measurement not yet standardized
• Assays- Diagnostic System Lab (DSL), Immuno-Tech Beckman-Coulter (IBC)
• Dispute on lower and higher level
• Poor correlation with oocytequality
Ovarian Responsiveness
AMH to predict Ovarian Responsiveness
• Correlates with number of oocytes retrieved
• Predictive value better than FSH, Inhibin B, E2
• Predictive value equal to AFC
• AMH <1.0 ng/ml- High chance of cycle cancellation
• AMH >4.0 ng/ml- High risk of OHSS
• Role in predicting ongoing pregnancy is limited
• Correlates with higher number of D2/3 embryos and better embryo morphology score
• High AMH correlates with higher live birth rate
Aflatoonian A, et al. 2009
Nelson SM, et al. 2009
Fleming R, et al. 2006
Ovarian Ageing
AMH Screening for Ovarian Ageing
• Earlier marker and more sensitive for POF than FSH
When to screen for Ageing
• Family H/O POF
• High Risk of POF
• Cancer Treatment
• Endometriotic Cystectomy
AMH in Male
AMH Screening in Male
• Secreted from Sertoli Cells
• Under control of gonadotrophins, suppressed by testosterone
• Serum AMH remains high until onset of puberty
• Value remains low in adult male
• Important in childhood to screen for hypogonadism
• Low AMH at puberty → Precocious puberty
• High AMH at puberty → Delayed puberty
Possible Role in Azoospermia
• AMH- OA < NOA
• Marker (Noninvasive) of successful sperm retrieval in OA
• Normal AMH in Sertoli-cell-only Syndrome
Number or Value
Low AMH = Poor Ovarian reserve???
Ovum Donation IVF DHEA Clinical Correlation
Conclusion
• Good predictor of ovarian reserve
• Predicts ovarian response to Gn Stimulation
• Predicts the probability of cycle cancellation and hyper-response in ART
• Levels are higher in PCOS
• Could be a potential marker of obstructive azoospermia
• Role as isolated marker- ?