The document discusses the optimal timing for administering hCG during fertility treatments. It states that the crucial step is identifying the best time to trigger ovulation. The timing depends on follicle size, serum estradiol levels, and endometrial thickness, with follicle size being the primary criteria. For gonadotropin cycles, follicles are considered mature at 15-18 mm for GnRH antagonists and 18-20 mm for GnRH agonists. hCG is used to trigger ovulation as it substitutes for the LH surge and controls the timing of procedures like sperm injection. Ovulation typically occurs 38-40 hours after hCG injection. The timing of sperm injection, intrauterine insemination, and egg

1. HCG timing
Prof Aboubakr Elnashar
Benha university Hospital, EgyptAboubakr Elnashar

2. Ovulation trigger
The end point of any ovulation induction protocol is to
indentify the best time for triggering ovulation.
 Most crucial step
Critical timing for HCG administation depends on the
criteria for follicular maturity
1. Follicular diameter
2. Serum E2
3. Endometrial thickness
 Always time HCG with follicle size
Gnt follicles mature at 15-18 mm
CC follicles mature at 18-20 mm
(Sperof,f 2005)
Aboubakr Elnashar

3. HCG ovulation triggers
substitute for LH surge seen in spontaneous
menstrual cycles
Control the timing of ovulation
Timing of SI.
Timing of IUI
Timing of OR
HCG has a half-life of about 35 h: support the
initial part of the luteal phase.
Aboubakr Elnashar

4. HCG
similar activity to LH and binds to its receptor.
 capable of inducing luteinization and ovulation.
Ovulation: 38 to 40 h after HCG injection.
 2 types: urinary and recombinant
Urinary HCG dose: 5000-10,000 IU, IM.
Recombinant HCG:
Dose: 250 mcg, SC.
similar pharmacokinetics as the u HCG: ovulation
is expected following a similar time interval.
Aboubakr Elnashar

5. Preparation Trade name Route U.pr Price Company
Urinary
HCG Pregnyl
Profasi
IM 95% Organon
Serono
H.P.HCG Choriomon SC,
IM
<5% Ibsa
Recombinant
HCG Ovitrelle
Choriogonadotropi
n
SC - Serono
LH Luveris
lutotropin
SC - Serono
Types of HCG
Aboubakr Elnashar

6. I. Timing SI
 Rationale:
 Viable spermatozoa should be present in the female
genital system at the time of ovulation.
 Sperms retain their fertilizing capacity for 40-80 h,
oocyte have life span of 12-24 h after ovulation.
 SI
 between 2 days before & the day of ovulation:
Highest conception rate
 On the day after ovulation: conception is zero.
≥24 h after ovulation then oocyte has already
degenerated.
Aboubakr Elnashar

7. CC:
Spontaneous ovulation can be expected when
the lead follicles 18-20 mm.
HCG trigger: when 1-2 follicle(s) is at a mature
size (18-20)
It is very important to avoid stimulation of too many
mature (or close to mature) follicles because of the
OHSS
ovulation can be induced with HCG) or (GnRHa).
Aboubakr Elnashar

8. Cochrane Database of Systematic Reviews
2013
Evidence is inadequate to recommend or refute
the use of u hCG as an ovulation trigger in
anovulatory women treated with CC
No trials evaluating the use of ovulation triggers
in anovulatory women treated with other
ovulation-inducing agents.
Aboubakr Elnashar

9. II. Timing IUI
 IUI should be performed around the moment of
ovulation. Since spermatozoa and oocytes have only
limited survival times correct timing is essential.
 Methods for timing of ovulation:
1. Urinary LH surge: In natural cycles:
Follicular rupture occurs 36 h after the onset of serum LH rise.
A positive urine result is often found only 12 h after the onset of
LH surge in the serum (around the point of serum LH peak).
Serum LH surge >25mIU/ml
 ovulation must be expected to occur on average as early as
24 h, after a positive urine test. If one adds a fertilizing life
span for the ovulated ovum of only 12 h to be on the safe
side, IUI 36 h after positive urine test is very satisfactory.Aboubakr Elnashar

10.  Serum LH surge: 12 h
Urine LH surge (serum LH peak): 24 h
Follicular rupture
lunch-time (11.0-15.00) is the best time to check for
the LH surge using urine dipsticks and insemination at
any time between 18 and 53 h after the onset of the
surge will produce optimal results
(Khattab et al, 2005).
A spontaneous LH surge was noted in a variety of
follicular sizes (14 to 35 mm)
(Vlahos et al, 2005)
Aboubakr Elnashar

11. 2. U/S and HCG triggering
a. Follicles:
The exogenous HCG mimics the endogenous LH surge
& offers the advantages that the onset of LH surge is
known precisely.
• HCG is given when the leading follicle is 17-20 mm.
• HCG should be withheld if
> 3 follicles > 16 mm:
(Macklon et al, 1999).
>4 follicles ≥ 14 mm
(Kamrava et al., 1982; Hugues et al., 2006).
Aboubakr Elnashar

12. b. Endometrial thickness:
<6 mm: No pregnancies
9-10 mm or more: The chance of pregnancy is great
(Isaacs et al, 1996).
Aboubakr Elnashar

13. 3. E2 peak (pg/ml):
<200
pregnancies are rare
500-1500
optimal
1500-2000
risk of OHSS is significant
>2000 pg./ml:
hCG is not given
Cyle is cancelled
(Speroff et al, 2006).
Aboubakr Elnashar

14. Chochrane. 2010 Cantineau et al
No significant differences between different
timing methods for IUI expressed as live birth rates:
hCG Vs LH surge
uhCG Vs rec hCG
hCG Vs GnRHa
The choice should be based on
hospital facilities
convenience for the patient
medical staff
Costs
drop-out levels.
Since different time intervals between hCG and IUI did
not result in different pregnancy rates, a more flexible
approach might be allowed.
Aboubakr Elnashar

15. 24 0r 36 H after HCG
IUI 36 h after hCG has marginally better pregnancy
rates than 24 h.
Timing of insemination may be kept at 24 or 36 h
after hCG injection to suit the convenience of the
clinic or care provider.
(Rahman et al, 2011)
Aboubakr Elnashar

16. HCG 34-36 h before or after IUI
HCG after IUI: more closely resembles the
fertilization process in natural cycles.
PR were 10 and 12 % (P = 0.85), respectively.
HCG administration after IUI brought about no
improvement in PR.
HCG can be administered either before or after IUI.
(Firouzabai et al, 2013, Aydin et al, 2013)
Aboubakr Elnashar

17. III. Before OR
Ovulation occurs 35-42 h after the onset of LH surge
which trigers resumption of meiosis inside the oocyte:
OR is scheduled for at least 35 h after HCG
HCG: 3 or more follicles of size ≥17 mm
Aboubakr Elnashar

18. Timing of hCG in IVF/ICSI protocols using
GnRH agonist or antagonists: a systematic
review and meta-analysis
Chen et al, 2014
1295 participants were included.
Early Vs 24 –h late HCG
The prolongation of follicular phase by delaying
hCG administration could increase E2, P levels and
oocyte retrieval, which will not influence PR per
oocyte pick-up, miscarriage rate and live birth rate.
Postponing hCG may enable increased flexibility
of cycle scheduling to avoid weekend procedures.
Aboubakr Elnashar

19. Devroy et al, 2009
Aboubakr Elnashar

20. Thank You
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Aboubakr Elnashar