Middle East Fertility Society Journal (2014) 19, 183186

Middle East Fertility Society

Middle East Fertility Society Journal

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ORIGINAL ARTICLE

Eect of postponing hCG injection after

intrauterine insemination on pregnancy rate
Mostafa S. Mostafa, Ahmed M. El Huseiny, Badeea S. Soliman *,
Marwa M. Mohammed
Obstetrics & Gynecology, Faculty of Medicine, Zagazig University, Egypt
Received 28 May 2013; accepted 13 October 2013
Available online 21 November 2013

KEYWORDS
Intrauterine insemination;
hCG;
Timing;
Pregnancy rate

Abstract Objective: During natural cycles, the best chance to become pregnant is if intercourse
occurs up to 6 day window ending on the day of ovulation. However, in the current practice, the
insemination is performed 3236 h after hCG injection when the ovulation is expected. The aim
of this study was to compare the effect of postponing hCG injection till after intrauterine insemination with current practice protocol, on pregnancy rate. Design: a prospective, randomized, controlled trial. Setting: Zagazig University hospital.
Materials and methods: This study included one hundred infertile couples with unexplained infertility that had been scheduled for articial insemination by husband semen. Women were divided into
two groups: the study group, including fty women in whom hCG was injected 35 min after IUI
(hCG after IUI) and the control group, including fty women in whom hCG was injected 2432 h
before IUI (hCG before IUI). Pregnancy test was done 2 weeks after insemination.
Results: The overall pregnancy rate in this study, following IUI was 9%. The pregnancy rate was
10% 5/50 in the study group (hCG after IUI), versus 8% 4/50 in the control group (hCG before
IUI). However, this difference is not statistically signicant.
Conclusion: There is no difference in pregnancy rate between HCG injection immediately following IUI and standard hCG injection 2432 h before IUI.
2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.

Introduction

* Corresponding author. Tel.: +20 553482142, mobile: +20

1222360673.
E-mail address: badia_seliem@yahoo.com (B.S. Soliman).
Peer review under responsibility of Middle East Fertility Society.

Production and hosting by Elsevier

Unexplained infertility usually refers to a diagnosis made in

couples in whom all the usual investigations such as tests of tubal patency, ovulation and semen analysis are normal. There is
no consensus about the role of IUI in the treatment of unexplained infertility particularly regarding its superiority in
unstimulated, stimulated cycles or timed intercourse (1).
The rational for the use of IUI in the management of
unexplained infertility is deposition of a bolus of prepared,

1110-5690 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.
http://dx.doi.org/10.1016/j.mefs.2013.10.002

184
concentrated, motile, morphologically normal sperm as close
as possible to oocyte (2).
Ovulation usually takes place from 24 to 56 h after the onset of the natural LH surge with a mean time of 32 h (3). However, oocytes can only be fertilizable 6 h after ovulation. This
means that even if spermatozoa meet the oocyte in the fallopian tube at the time of ovulation there are still 6 h to the fertilizable period of the oocytes to start. Additionally, oocyte is
fertilizable for only, a period of 1216 h after ovulation (4).
Based on the above, IUI should be done after observation of
ovulation for this reason, in the majority of IUI studies; the
insemination is performed 3236 h after hCG injection (5).
However it appears that among healthy women, the best
chance to become pregnant is if intercourse occurs up to 6 days
before ovulation (6). If this is applied to intrauterine insemination protocol, the hCG should be injected after the insemination rather before it. Therefore, this comparative study was
designed to study the effect of postponing hCG immediately
after IUI rather than 32 h before it (standard method) on pregnancy rate.
Patients and methods
This is a prospective randomized controlled study that was
conducted in Assisted Reproductive Technologies (ART),
Cytogenetic Unit (CGU), Zagazig University Hospital during
the period between October 2010 and September 2011. The
study included one hundred infertile couples with a diagnosis
of unexplained infertility who had been scheduled for intrauterine insemination (IUI) by husband semen. Unexplained
infertility was dened based on the following criteria:
(1) Satisfactory seminal analysis according to WHO reference values on 2010 (7).
(2) Bilateral patent tubes were based on hysterosalpingography and/or laparoscopy.
(3) Normal ovulation as evidenced by regular menstrual
cycles and mid luteal serum progesterone levels
>10 ng/ml.
The following inclusion criteria were also, adopted: the age
of female partner is less than 37 years, a normal basal hormonal prole (FSH, LH, TSH, E2 and Prolactin) and a satisfactory basal (day-2) transvaginal ultrasound examination.
Cases with failed previous 3 IUI trials were excluded from
the study. All patients gave informed consent and the study
was approved by local ethics committee for scientic research.
Combined sequential protocol; Clomiphene Citrate 100 mg
from days 3 to 7 of menstrual ow followed by Human Menopausal Gonadotropins (hMG) (Menogon, Ferring) 75
150 IU/day. Serial TVS assessment of follicular growth and
endometrial thickness was started from cycle day 7 till a mean
follicular diameter of 1718 mm was reached. Selection was
done according to denite criteria, but assignment into two
groups was divided randomly by using random table (computer software Open Epi version 3.21): group (1); study group:
50 women in whom hCG (10,000 IU) was injected 35 min
after IUI. Group (2); control group: 50 women in which
hCG (10,000 IU) was injected 2432 h before IUI.
The double wash swim up technique using Hams F10
culture media was used for sperm preparation in all cases.

M.S. Mostafa et al.

The nal sperm pellet was suspended in a total of 0.5 ml sperm
wash media. The following post-processing sperm criteria were
adopted in this study: A sperm count more than 10 million per
ml and sperm motility grade (a) and (b) more than 50%. The
washed sperm sample was loaded into a IUI catheter, which
was inserted through the cervical canal and into the uterine cavity. Immediately following the IUI the patient was discharged
and normal activity could be resumed. Luteal phase support
by vaginal progesterone suppositories 200 mg (Prontogest,
GMP Marcyrl) twice daily was started at day of insemination
and continued for 2 weeks later when a pregnancy test was
scheduled.
Statistical analysis
Data were reported as mean and standard deviation
(Mean SD). Differences between groups were tested using
Students t test and A chi-squared (X2) test. A chi-squared
(X2) test was used to assess the statistical signicance when
the incidence of primary and secondary infertility as well as
occurrence of pregnancy was compared. The chosen level of
signicance was p < 0.05.
Results
Between October 2010 and September 2011, one hundred women who had been scheduled for IUI were studied. Table. 1
shows basic characteristics and basic hormonal prole of both
groups. There were no statistically signicant differences
regarding mean age, duration and type of infertility as well
as serum level of FSH, LH, TSH and prolactin. Similarly,
there were no statistically signicant differences in the post
processing seminal parameters (count, motility and abnormal
forms) between both groups (Table 2).
Table 3 shows pelvic ultrasound data at day of hCG injection. No statistically signicant differences were reported
regarding the mean diameter and number of dominant follicle
nor endometrial thickness between both groups. A positive
pregnancy test was yielded in 5 women (10%) in group 1
(hCG after IUI) and 4 women (8%) in group 2 (hCG before
IUI). This was not a statistically signicant difference (Table 4).
Discussion
Intrauterine insemination (IUI), together with ovarian stimulation, is a less expensive and invasive treatment in comparison
with other assisted reproductive techniques (8). Traditionally,
the insemination has been performed 2436 h following hCG
administration (5,9). This practice is based on dictum that,
in natural cycles, the ovulation takes place 32 h (range 24
56 h) after the onset of the luteinizing hormone (LH) surge
(10), whereas in stimulated cycles, it takes place approximately
3638 h after the hCG injection (11).
As the current assumption is that the oocytes are fertilizable
for a limited period of time in the female reproductive tract
(1214 h), it is rational to schedule the insemination to the time
of expected ovulation, i.e., 2436 h after the administration of
hCG. However, the study done by Wilcox et al. (6) suggested
that conception occurred only when intercourse took place
during a six-day period that ended on the estimated day of

Intrauterine insemination, postpone hCG, pregnancy rate

Table 1

Basic characteristics of both groups.

Age (years) Mean SD (range)

Duration of infertility Mean SD (range)
Type of infertility primary secondary
Basal FSH (IU) Mean SD range
Basal LH(IU) Mean SD range
TSH (IU) Mean SD range
Prolactin (ng/ml) Mean SD range

Table 2

185

hCG after IUI

hCG before IUI

28.3 4.7 (1936)

2.28 1.5 (17)
36 (72%) 14 (28%)
7.4 1 (5.38.5)
4.7 1.4 (3.28.2)
2.45 0.87 (1.154.5)
11.67 3.8 (5.422)

26.6 4.2 (1736)

2.7 1.69 (18)
39 (78%) 11(22%)
7.2 1.4 (3.88.6)
5.2 1.6 (2.28.6)
2.33 0.74 (1.154.3)
12.16 5 (4.522.6)

1.57
1.71
X2 = 0.4
1.88
1.79
0.77
0.55

0.11
0.6
0.48
0.6
0.07
0.43
0.58

Post processing seminal parameters of both groups.

Post processing semen parameter

hCG after IUI

hCG before IUI

Sperm count (mil./ml) Mean SD (range)

Sperm motility (%) Mean SD (range)
Abnormal forms (%) Mean SD

28.67 9.71 (1248)

64.733 7.33 (5377)
63.5 15.6 (3580)

32.95 4.63 (1455)

67.06 8.41 (5579)
66.75 17.9 (4585)

0.18
0.97
0.96

0.84
0.33
0.34

Table 3

Pelvic ultrasound data of both groups at time of hCG injection.

TVS at day of hCG

hCG after IUI

hCG before IUI

Endometrial thickness Mean SD/mm (range)

Number of follicles Mean SD (range)
Mean follicle diameter Mean SD/mm (range)

9.2 2.3 (79.6)

1.8 0.5 (13)
18.12 1.48 (1622)

8.7 2.0 (6.89.4)

1.78 0.5 (13)
18.2 1.4 (1621)

1.88
0.19
0.64

0.17
0.84
0.52

Table 4

Comparison between group I and group II according to pregnancy test result.

hCG hCG after IUI

Pregnancy test +ve (N%)

Pregnancy test ve (N%)
Total
X2
P-value

5
4
50
0
>0.05 NS

(10%)
(90%)
(100%)

ovulation. This nding suggests that the chances to conceive in

the natural cycle diminish considerably after ovulation and
that, preferably, the spermatozoa should be available in the
reproductive tract before ovulation occurs. If this is applied
to IUI protocol, hCG should be injected after the insemination
rather than before it. This study was carried out to test this
notion.
Our study, a randomized controlled one aimed to evaluate
the effect of postponing the hCG injection until after IUI on
pregnancy rate. The overall pregnancy rate reported in this
study was 9%. This matches with overall pregnancy rates (8
22%) following IUI reported in other studies (5,12,13). For
each group, the pregnancy rate was 10% [5 pregnancies in
group (1)] when hCG was administered after IUI versus 8%
[4 pregnancies in group (2)] when hCG was administered before IUI. Therefore, postponing the hCG administration till
after the IUI resulted in a higher though, non-signicant pregnancy rate.
A recent study was carried out by Dehghani-Firouzabai
et al. (14) on 100 infertile couples, in which they were divided
into two groups; hCG injection before IUI and hCG injection
after IUI. The main outcome measure was the pregnancy test

hCG hCG before IUI

Total

4
46
50

9
91
100

(8%)
(92%)
(100%)

that was done 2 weeks after the insemination. They found no

improvement in the pregnancy rate with hCG administration
after IUI, therefore, hCG can be administered either before
or after IUI.
Compared to our results, Jervela et al. (15) reported a signicantly higher pregnancy rate when hCG was administered
immediately after IUI (19.6%) than when administered 24
32 h before IUI (10.9%). This signicantly higher pregnancy
rate in that study can be attributed to the retrospective comparison of the results of the new protocol (hCG after IUI) with
those of standard protocol hCG before IUI for cases done
2 years before hand. This may involve changes of the media
used or better techniques of IUI in the new protocol with possible better pregnancy end results.
According to the results of this current study, the overall
pregnancy rate following IUI did not signicantly differ if
hCG is administered immediately after IUI compared to standard protocol hCG injection 2432 h before IUI. This may
allow for more exibility of IUI protocols and more convenience of infertility clinic staff. However, larger multi-centric
studies are still required before recommending adoption of this
new protocol.

186
In conclusion, there is no difference in pregnancy rate between hCG injection immediately following IUI and standard
hCG injection 2432 h before IUI.
Conict of interest
We declare that no actual or potential conict of interest in
relation to this article exists.

Acknowledgements
The authors would like to thank staff members of cytogenetic
unit as well as all women for their valuable contribution in this
work.
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