LH – FSH Deficiency: An introduction

Budi Wiweko
budi.wiweko01@ui.ac.id
budi.wiweko@gmail.com

Academic Health System Universitas Indonesia - Indonesian Medical Education and Research Institute
Faculty of Medicine Universitas Indonesia
Dr. Cipto Mangunkusumo General Hospital
Jakarta

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 PATIENTS ENDOMETRIUM

OVARIAN STIMULATION EMBRYO TRANSFER

EMBRYO OTHERS

R S
A C TO
Y F
KE IVF SUCCESS

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 Reproductive Biomedicine Online - 2011

Current opinion on use of luteinizing hormone

supplementation in assisted reproduction therapy: an Asian
perspective
Peng Cheang Wong, Jie Qiao, Clement Ho, Gottumukkala A Ramaraju, Budi Wiweko,
Yuji Takehara, Prashant V Nadkarni, Li-Chang Cheng, Hsin-Fu Chen, Somchai
Suwajanakorn, Thi Ngoc Lan Vuong

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The strongest predictive factors for
need exogenous LH in ART
1. Previous poor ovarian response
2. Sub-optimal ovarian response during stimulation

• no follicle > 10 mm by day 6 – 8

• low estradiol (< 180 pg / ml) by day 6
• poor progression or slowing of follicle growth, with previously 1 – 2 mm
progression per day slowing to less than 2 mm in 3 days
• women above 35 years old

Wong et al. Reprod Biomed Online, 2011

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……..update the issues……..

1 LH therapeutic window

2 severe endogenous LH deficiency

3 patient sub-population

4 exogenous LH supplementation

5 dose and timing of supplementation

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 THE LH
WINDOW
Suppression of granulosa cells proliferation
Follicular atresia
Premature luteinization (pre-ovulatory follicle)
Oocyte development compromised

LH CEILING
Normal follicular growth and development
Paracrine signalling activated by FSH and LH receptor
Adequate granulosa proliferation and functional maturation
Normal androgen and estrogen synthesis
Full follicular and oocyte maturation

LH THRESHOLD
No paracrine signalling between granulosa and theca cells
No androgen and estrogen synthesis
No full oocyte maturation

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severe endogenous LH deficiency

• Although ovarian stimulation is efficiently achieved in most cases by the

administration of exogenous FSH alone, specific subgroups of women may
benefit from LH activity supplementation during ovarian stimulation

• 10−12% of young normogonadotrophic patients treated with a

gonadotrophin-releasing hormone agonist (GnRH-a), a ‘steady response’ is
observed
Carlo Alviggi

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What is severe endogenous LH deficiency ?

1. Anovulation WHO I
2. Steady response group

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Let us………………………

START LECTURE AND DISCUSSION

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 SOME INTERESTING POINTS

1. 10–12% of patients may fail to respond adequately to ovarian stimulation Presumably

these patients lack adequate concentrations of endogenous LH after pituitary down-
regulation

2. Clinicians only have few tools available to identify either before or during ovarian
stimulation which patients may benefit from additional LH activity

3. Whatever type of LH activity is used in ovarian stimulation, it is clear from studies in

hypogonadotropic patients that 75 IU of LH activity has demonstrable biological activity

4. LH supplement use in GnRH agonist or antagonist cycles is done due to the profound and
rapid LH suppression that occurs at a time in follicle development dominated by LH
activity

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The POSEIDON Criteria and Its Measure of Success Through the Eyes of
Clinicians and Embryologists

Esteeves et al. Frontiers Endocrinol, 2019

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Haahr et al. Reprod Bio endocrinol, 2018

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The strongest predictive factors for
need exogenous LH in ART
1. Previous poor ovarian response
2. Sub-optimal ovarian response during stimulation

• no follicle > 10 mm by day 6 – 8

• low estradiol (< 180 pg / ml) by day 6
• poor progression or slowing of follicle growth, with previously 1 – 2 mm
progression per day slowing to less than 2 mm in 3 days
• women above 35 years old

Wong et al. Reprod Biomed Online, 2011

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 TAKE HOME MESSAGES

1. The importance of LH in the biological process of follicular development and

oocyte maturation should not be forgotten

2. The assisted reproduction practitioner should always bear the importance of

adequate LH stimulation in mind

3. Methods for identifying patients who are most likely to benefit from LH
supplementation should be developed (pre or intra stimulation parameters)

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THE OBJECTIVE OF LH SUPPLEMENTATION

MAINTAIN OPTIMAL LH ENDOGEN

ADEQUATE OVARIAN RESPONSE

• Good quality of oocytes
• Good quality of embryos
• Pregnancy

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 Acknowledgement
Ichramsjah AR, TZ Jacoeb, Soegiharto Soebijanto, Ali Baziad, Andon Hestiantoro, Muharam Natadisastra, Kanadi Sumapraja, Budi Wiweko,
Gita Pratama, Herbert Situmorang, Achmad Kemal, Eliza Mansyur, Tita Yuningsih, Dyah Pitha, Siti Maryam,
Endang Purdiningsih, Lady Margaretha, Anesia Tania, Nadia Safira, Tri Septriyani, Kresna Mutia, Rima Meyana, Laily, Gita

Indonesian Reproductive Medicine

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