This study compared outcomes of IVF cycles stimulated with either recombinant LH (r-hLH) or human menopausal gonadotropins (hMG) acting as an LH analogue in subjects with good or poor ovarian reserve. The study found that in subjects with good ovarian reserve, as indicated by baseline FSH <10 IU/L and AFC ≥6, r-hLH resulted in significantly lower FSH dose, lower LH dose, higher oocyte yield, higher embryo yield, and higher pregnancy and clinical pregnancy rates compared to hMG. No significant differences were observed between r-hLH and hMG in subjects with poor ovarian reserve.

1. A comparison of outcomes from in vitro fertilization cycles stimulated
with either recombinant luteinizing hormone (LH) or human
chorionic gonadotropin acting as an LH analogue delivered as
human menopausal gonadotropins, in subjects with good or poor
ovarian reserve: A retrospective analysis
Michael H. Dahan *, Mohammed Agdi, Fady Shehata, WeonYoung Son, Seang Lin Tan
McGill Reproductive Center, McGill University, Royal Victoria Hospital, Montreal, Canada
European Journal of Obstetrics & Gynecology and Reproductive Biology 172 (2014) 70–73
Anna Hnug
Product Manager
Feb 17th, 2014

2. Background information
- Addition of LH may benefit certain patients
有些特性的病人加入LH後可以
促進濾泡發育(folliculargenesis)
及增加懷孕率
• 年齡較大(>35 yr)
• Poor responder
• Very low serum LH level
在幾個meta-analysis中可看到，
LH+FSH的protocol比FSH
alone的protocol
• 懷孕率較高
• 臨床懷孕率較高
• 活產率較高
• 著床率較高(r-hLH)
• 使用FSH的劑量較少(agonist
long protocol)
• 取得較多的卵(antagonist
protocol)

3. LH & follicle maturation
雖然LH level在late follicular phase才昇高，但在early & mid follicular
phase時LH有助於濾泡成熟( &selection of dominant follicle)

4. Background information: r-hLH vs. hMG

5. 探討問題
需要LH的IVF病人
-包括卵巢庫存量較少且使用microdose
flair protocol的IVF病人族群
r-hLH hMG
何者效果較佳？

6. Materials & Methods - medications
單一中心回溯性研究
Patients undergoing IVF
•Including:
- Received FSH and either r-hLH
or HMG (not both)
•Excluding:
-Thyroid abnormalities
-Hyperprolactinemia
-Hypothalamic pituitary
dysfunction
-Ovarian failure
n=105
r-FSH (Gonal-f) +
r-hLH (Luveris)
r-FSH (Gonal-f/Puregon)/urofollitropin +
hMG (Repronex*)
2-year period n=96
Total n=201
Indicators include:
Total FSH dose Oocytes obtained Pregnancy rate
Total LH dose Embryos obtained Clinical pregnancy rate
* Repronex: Ferring Inc. North York , Canada)

7. Materials & Methods - protocols
n=122
Good ovarian reserve
baseline FSH <10 IU/L
and
baseline AFC ≧6
Poor ovarian reserve
baseline FSH≧10 IU/L
or
baseline AFC < 6
n=79
GnRH agonist long protocol
112.5~225 IU/daily
*Microdose flair protocol
n=105
r-FSH (Gonal-f) +
r-hLH (Luveris)
r-FSH/urofollitropin +
hMG (Repronex)
n=96
• Trigger: 10,000IU or 5,000IU hCG
• Retrieval & ET:
17 gauge single lumen needle or
16 gauge double lumen flushing needle
300~600 IU/daily
*Microdose flair protocol

8. Results (Table 1)
Patient demographics 兩組相當
Recombinant
h-LH
hMG p-value
Number of cycles 105 96 –
Age (years) 36.2 ± 4.1 36.7 ± 4.4 0.39
Day 3 serum FSH (IU/L) 9.3 ± 7.4 8.9 ± 3.3 0.57
Day 3 serum estradiol (pmol/L) 180 ± 98 200 ± 118 0.22
Antral follicle count 14 ± 10 12 ± 7 0.11
Previous pregnancies 0.8 ± 1.1 1.0 ± 1.1 0.18
Previous full term pregnancies 0.2 ± 0.5 0.26 ± 0.7 0.22
Previous miscarriages 0.6 ± 0.9 0.7 ± 0.8 0.40

9. Results (Table 2)
Infertility原因僅tubal disease有顯著差異
Infertility diagnosis r-hLH group hMG group p-value
Number of cycles 105 96 –
Male factor 50% 42% 0.24
Endometriosis 8% 13% 0.24
Genetic disease carrier 5% 9% 0.30
PCOS 7% 1% 0.10
Tubal disease 7% 17% 0.02*
Unexplained 28% 23% 0.38
*Since patients may have more that one infertility diagnosis, the diagnostic rates total >100%.

10. Results (Table 3)
IVF treatment outcomes 比較
r-hLH hMG p-value Comments (r-hLH組)
Number of cycles 105 96 –
Total FSH dose (IU) 3944 ± 1820 4783 ± 2100 0.003* 使用較少的FSH
Total LH dose (IU) 1601 ± 952 2354 ± 1784 0.0001* 使用較少的LH
Oocytes obtained 12 ± 7 10 ± 6 0.008* 得到較多的卵
Embryos obtained 7 ± 5 5 ± 3 0.009* 得到較多的胚胎
Percent of ICSI cases per group 75% 82% 0.23
Pregnancy rate per cycle start 42% 26% 0.03* 較高的懷孕率
Clinical pregnancy rate, per cycle
start
36% 20% 0.02* 較高的臨床懷孕率

11. Results (Table 4)
依照卵巢庫存量指標比較r-hLH vs. hMG有無顯著差異(p-value)
good good poor poor
Baseline FSH
<10 IU/L
Baseline
AFC ≥ 6
Baseline FSH
≥10 IU/L
Baseline AFC
<6
r-hLH (n) 78 88 27 17
hMG (n) 68 82 28 14
Total FSH dose (IU) 較少0.003* 0.002* 0.35 0.15
Total LH dose (IU) 較少0.001* 0.001* 0.09 0.21
Oocytes obtained 較多0.01* 0.002* 0.33 0.44
Embryos obtained 較多0.03* 0.007* 0.16 0.63
Pregnancy 較高0.12 0.01* 0.15 1.0
Clinical pregnancy 較高0.18 0.02* 0.04* 1.0
•在good ovarian reserve (FSH < 10IU/L ; AFC ≥ 6)的病人,
r-hLH gr.的表現顯著優於HMG(取得較多卵、較高懷孕率)

12. Recombinant human LH supplementation versus
supplementation with urinary hCG-based LH activity during
controlled ovarian stimulation in the long GnRH-agonist protocol: a
matched case–control study
Klaus F. Bühler1 & Robert Fischer2
1Kinderwunschzentrum Hanover-Langenhagen & Wolfsburg, GMP Müseler-Albers/Arendt/Bühler/Schill,
Langenhagen, Germany and
2Fertility Center Hamburg, Hamburg, Germany
European Journal of Obstetrics & Gynecology and Reproductive Biology 172 (2014) 70–73

13. Materials & Methods - medications
r-hFSH + r-hLH (2:1)
(n=1573)
hMG alone
(n=1573)
hMG + r-hFSH
(n=1573)
long GnRH-agonist protocol
(n=4719)
與另兩組相比：
• r-hFSH使用量較少
• 懷孕率較高
• 胚胎植入著床率較高
• 2007 Oct.~2009 Jun.
• Data collected using RecDate electronic
database

14. Results (Table 1)
Patient demographics 兩組相當

15. Results (Table 2)
r-hLH+r-hFSH gr. FSH 使用劑量顯著較低

16. Results (Table 3)
r-hLH+r-hFSH , ≦35 yr sub gr. 的implantation
rate per ET 顯著較高(24.8% vs. 17.2% & 17.5%)

17. Discussion
 The pts population analysed can be regarded as representative for
routine ART treatment in Germany
 r-hLH (in combination with r-hFSH) 比u-hMG 的懷孕率顯著較高(per
cycle and per ET); 著床率顯著較高(per ET)
 Age subgroup analysis: r-hLH 對於小於35歲的pts, 有較明顯的效益

18. Information sharing:
Current standard luteal phase support in
NTUH

19. TNUH current standard luteal phase support
• For fresh IVF cycle, Estrade (2 mg) 3 bid and Crinone 1 bid
for follicle number > 10 or for all cases
• For fresh IVF cycle, Utrogestan (100 mg) 1 tid or Crinone 1 qd,
plus Pregnyl (hCG 1500 IU) q3d, 3 doses, for follicle number < 10
• For frozen ET with natural cycle, Crinone 1 qd
• For frozen ET with HRT* cycle, Crinone 1 bid
* HRT: Hormone Replacement Treatment

20. Starting time and duration of the luteal phase
support
• For the fresh IVF cycle, start since 2 days after OPU (2-4 cell stage)
- After pregnancy test, if the corpus lutein is rescued, stop the LPS gradually.
- If the corpus lutein is not rescued, continue to GA 12 weeks.
• For frozen ET with natural cycle, start since 2 days after ovulation (2-4 cell stage).
- Stop LPS after pregnancy test or continue to GA 7-9 weeks.
• For HRT cycle, the day of LPS is defined as ovulation day,
- continue to GA 12 weeks.

21. Early pregnancy / Extend the luteal support
• For the fresh IVF cycle,
- If the corpus lutein is rescued, taper and then stop the LPS at GA 5 weeks.
-If the corpus lutein is not rescued, continue to GA 12 weeks.
• For frozen ET with natural cycle,
- stop LPS after pregnancy test or continue to GA 7-9 weeks.
• For HRT cycle, continue to GA 12 weeks.

22. Feedback on Crinone
• Good results
• No pain, No dizziness
• Reduce OHSS
• Some with itching, not common