HCG timing Prof Aboubakr Elnashar

Benha university Hospital, Egypt Aboubakr Elnashar

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)

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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.

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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.

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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

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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.

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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).

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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.

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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

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)

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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).

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b. Endometrial thickness:

<6 mm: No pregnancies

9-10 mm or more: The chance of pregnancy is great (Isaacs et al, 1996).

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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).

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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.

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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)

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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)

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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

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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.

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Devroy et al, 2009 Aboubakr Elnashar

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