The document discusses luteinizing hormone (LH) structure and function, as well as its role in assisted reproduction. It summarizes evidence from multiple publications on using recombinant human LH (r-LH) as an adjuvant to recombinant FSH (r-FSH) in ovarian stimulation. The evidence is conflicting, but there is consensus that r-LH may benefit women with hypogonadotropic hypogonadism, those aged 35-39, those with a suboptimal response to r-FSH, and in reducing ovarian hyperstimulation syndrome risk. However, the optimal dose, timing and patient groups require more clarification.

3. Greetings from Assisted Reproduction
Unit – Qena faculty of medicine -
South Valley University

7. ➢ LH structure:
▪ LH is a glycoprotein hormone produced by the anterior
pituitary gland under control of GnRH.
▪ Its structure is similar to other glycoprotein hormones,
FSH, TSH, and human chorionic gonadotropin (hCG).

8. ➢ LH structure:
▪ It contains alpha and beta subunits. The alpha subunit is
identical to that of FSH, TSH, and hCG.

9. ➢ LH structure:
▪ The beta subunits vary. LH beta subunit confers its
specific biologic action and is responsible for the
interaction with the LH receptor. This beta subunit
contains an amino acid sequence that exhibits large
homologies with that of the beta subunit of hCG and both
stimulate the same receptor.
Jiang X, Dias JA, He X (January 2014). "Structural biology of glycoprotein hormones and
their receptors: insights to signaling". Molecular and Cellular Endocrinology

10. ➢ LH Function:
▪ At the time of menstruation, FSH initiates follicular
growth, by affecting granulosa cells.

11. ➢ LH Function:
▪ With the rise in estrogens, LH receptors are also
expressed on the maturing follicle, which causes more
estradiol production.

12. ➢ LH Function:
▪ Eventually, when the follicle has fully matured, a rise in
17α-hydroxyprogesterone inhibits more production of
estrogens, leading to a decrease in negative feedback
of GnRH in the hypothalamus, which then stimulates
the release of LH from the anterior pituitary.

13. ➢ LH Function:
▪ The levels keep rising through the follicular phase when
reach unknown threshold, this results in the peak of
the LH. "LH surge" that triggers ovulation not only
releasing the egg from the follicle, but also initiating
the conversion of the residual follicle into a corpus
luteum.

14. ➢ LH Function:
▪ Corpus luteum in turn produces progesterone to
prepare the endometrium for implantation.
▪ LH maintains luteal function for the second half of the
cycle. If pregnancy occurs, luteal function will be
maintained by the action of hCG which is very similar to
LH but secreted from the placenta..
Guyton and Hall ,Textbook of Medical Physiology 2006

18. ➢ In non-stimulated cycles Abnormal LH level →
dysovulation Syndromes:
▪High basal LH: follicular atresia.
▪Premature LH surge: luteinized unruptured follicle (LUF).
▪Absent LH surge: follicular cyst.
▪Low luteal LH: luteal phase defect (LPD).

19. ➢ In stimulated cycles:

20. Balasch, J., Vidal, E., Peñarrubia, J.et al. (2001). Suppression of LH during ovarian
stimulation: analysing threshold values and effects on ovarian response and the
outcome of assisted reproduction in down-regulated women stimulated with
recombinant FSH. Human Reproduction, 16(8), 1636-1643.

21. Humaidan, Peter, Leif Bungum, Mona Bungum, and C. Yding Andersen. "Ovarian
response and pregnancy outcome related to mid-follicular LH levels in women
undergoing assisted reproduction with GnRH agonist down-regulation and recombinant
FSH stimulation." Human Reproduction 17, no. 8 (2002):.

22. Balasch, Juan, and Francisco Fábregues. "Is luteinizing hormone needed for optimal
ovulation induction?." Current Opinion in Obstetrics and Gynecology 14, no. 3 (2002):
265-274.

23. O’Dea, Louis, Fanny O’Brien, Karen Currie, and George Hemsey. "Follicular development
induced by recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
in anovulatory women with LH and FSH deficiency: evidence of a threshold effect."
Current medical research and opinion 24, no. 10 (2008): 2785-2793.

24. Kumar, Pratap, and Sameer Farouk Sait. "Luteinizing hormone and its dilemma in
ovulation induction." Journal of human reproductive sciences 4, no. 1 (2011):

25. Vohra, Arveen & Rao, Kamini. (2014). Luteinizing Hormone in Controlled Ovarian
Stimulation. International Journal of Infertility & Fetal Medicine. 5. 75-86. 10.5005/jp-
journals-10016-1086.

26. Conrad, D., G. Hughes, and G. Sacks. "LH Supplementation for Low LH Levels during
Antagonist IVF Cycles Improves Live Birth Rates." JFIV Reprod Med Genet 3, no. 155
(2015): 22-24

27. Summary of different publications

30. ➢ For LH activity (LH and/or hCG molecules)
1.Human Chorionic Gonadotropin
▪ Recombinant – (r-hCG) 250 mcg=6750 IU of
LH, 99% pure
▪Urinary – (u-hCG) 5000–10,000 IU ≥50%
impurities

31. ➢ For LH activity (LH and/or hCG molecules)
2.Human Menopausal Gonadotropin
▪ hMG=75 IU FSH: 75 IU of LH activity, 95%
hCG derived and >30% impurities

32. ➢ For pure LH molecules
Recombinant human LH
▪ Alone (r-hLH) 75 IU, 99% pure
▪ Combination with rFSH (r-hFSH + r-hLH)
150:75 IU, 99% pure

35. Alviggi, Carlo et al.." Fertility and sterility 109, no. 4 (2018): 644-664.

36. ➢ 1st group → the hypo-responders:
▪ In Women with a Hyporesponse to Exogenous FSH
Monotherapy
▪ They are women with normal ovarian reserve who can
achieve adequate number of oocytes and more estradiol
production BUT they need a large dose of FSH ( ≥3000
IU) and more stimulation days
▪ They are either lacking of FSH receptors or less
sensitive to FSH.
De Placido G et al. Hum Reprod 2005;20:390–6.

37. ➢ 1st group → the hypo-responders:

38. ➢ 1st group → the hypo-responders:

39. ➢ 2nd group → Women with Advanced
Reproductive Age (35-39 years old):

40. ➢ 3rd group → women receiving GnRH Antagonist
protocol:

41. ➢ 4th group → Women with Severely Suppressed
LH Levels after Long GnRH-Agonist Down-
Regulation:

42. ➢ 5th group → r-LH for prevention of OHSS
▪ Only one RCT by Caserta et al. 2011 in which patients
were randomized to receive r-hFSH alone or r-hFSH +
r-hLH. A daily dose of 150 IU r-hFSH was administered
in both groups; r-hLH supplementation was given at a
dose of 75 IU/d from stimulation day 7 onward.
▪ No differences in age or mean number of embryos
transferred were observed between groups.
▪ the number of eggs retrieved was lower in the
supplemented group than in the r-hFSH–alone group

43. ➢ 5th group → r-LH for prevention of OHSS
▪ However pregnancy rate was higher in the
supplemented group than in the r-FSH–alone group
▪ the proportion of patients who developed clinical OHSS
were significantly higher in the r-hFSH–alone group
than in the r-hFSH + r-hLH group.
Caserta D et al. Gynecol Endocrinol 2011;27: 862–6.

44. ➢ 6th group → Women classified as poor
responders to ovarian stimulation:

45. ➢ Summary:

48. ➢ Confusing evidence
No benefit in unselected population
➢ “Consensus” for the following:
o Hypogonadotropic – hypogonadism
o advanced reproductive age (35 – 39 years)
o Suboptimal response to FSH
o Reduce the risk of OHSS
➢ Lack of consensus for:
Dose, timing, and start of r-LH
Role in poor responders