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\begin{document}

\title{Effect of HCG-triggered ovulation on pregnancy outcomes in intrauterine
insemination: an analysis of 5610 first IUI natural cycles with donor
sperm in China}



\author[1]{jipeng wan}%
\author[2]{ Zhen-Jing Wang}%
\author[2]{Yan  Sheng}%
\author[2]{Wei Chen}%
\author[2]{Qing-Qing  Guo}%
\author[2]{Jin  Xu}%
\author[2]{Hua-Rui  Fan}%
\author[2]{Mei Sun}%
\affil[1]{Shandong Provincial Hospital}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To evaluate the effect of human chorionic gonadotropin (hCG)
trigger ovulation on pregnancy outcomes in natural IUI cycles with donor
sperm. Design: Retrospective cohort study. Setting: Not applicable.
Patients: A total 5610 first-natural IUI cycles with donor sperm in
infertile couples during the period from January 2012 to December 2017.
To control for other confounding factors, our analysis was restricted to
normo-ovulatory women without tubal infertility. Intervention(s):
hCG-triggered ovulation Main Outcome Measures: The main outcome measure
was live birth rate; the secondary outcomes included rates of clinical
pregnancy and miscarriage. Results: In the crude analysis, both the
clinical pregnancy (27.40\% versus 22.73\%; P =0.001) and live birth
rates (24.52\% versus 20.13\%; P =0.007) were significantly higher for
the hCG group than for the spontaneous LH group. After adjustment for a
number of confounding factors, the reproductive outcomes were still
significantly worse for the spontaneous ovulatory group. Conclusions:
Among women undergoing natural cycle IUI with donor sperm, hCG triggered
ovulation for timing insemination offers beneficial impacts on both
clinical pregnancy rates and live birth rates.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Intrauterine insemination (IUI), a minimally invasive and low-cost
procedure, is a first-line treatment for a broad range of indications in
reproductive medicine \textsuperscript{1,2}. IUI involves timely
scheduled insemination of sperm into the uterus, either in natural
cycles or following ovarian stimulation. Compared to stimulated IUI,
natural cycle IUI is preferable for patients because of advantages
including lower medication cost and reduced rates of multiple
gestation\textsuperscript{3}.

It is known that the timing of insemination is one of the most impactful
factors influencing the success rates of IUI \textsuperscript{4, 5}.
There are various methods for timing IUI, and administration of human
chorionic gonadotropin (hCG) is a widely accepted in clinical practice.
Administration of hCG requires less endocrine monitoring, but its effect
on endometrial receptivity has drawn extensive attention
recently\textsuperscript{6- 8}.

Multiple clinical studies have assessed the effect of hCG on pregnancy
outcomes, but have reached inconsistent
conclusions\textsuperscript{9-12}. Such conflicting results result from
clinical indication, female age, baseline characteristics of study
participants, sperm quality, timing, or type of ovarian stimulation.

The current study examined a large cohort of women undergoing natural
cycle IUI and aimed to assess the effect of hCG-induced ovulation on
pregnancy outcome of natural cycles IUI. Attempting to control for
sperm-related factors, this retrospective study only examined patients
using donor sperm.

\textbf{Materials and Methods}

\textbf{Study Design}

This retrospective study included women who underwent IUI with donor
sperm in a natural menstrual cycle. The trial was conducted between
January 2012 and December 2017 at the Center for Reproductive Medicine
of the Shandong Provincial Hospital Affiliated to Shandong University.
The Institutional Review Board approved the research project.

Prior to the IUI cycles, all women underwent basic fertility
investigation that included evaluations of the following: cycle day 3
FSH, LH, estradiol, anti-M\selectlanguage{ngerman}üllerian hormone (AMH), prolactin, and thyroid
stimulating hormone (TSH) levels, hysterosonography (at least one month
prior to IUI), as well as transvaginal ultrasound for evaluation of
pelvic anatomy and follicular monitoring.

Study inclusion criteria were: age \selectlanguage{english}[?] 35 years, regular menstrual cycles
(28--35 days), no personal history of infertility or medical conditions
likely to cause infertility, a normal baseline hormonal profile, and
patency of at least one fallopian tube. Exclusion criteria were the
presence of irregular menstrual cycles, tubal factor infertility,
confirmed endometriosis, a diagnosis of polycystic ovarian syndrome
(according to the Rotterdam criteria; Rotterdam ESHRE/ASRM-Sponsored
PCOS Consensus Workshop Group, 2004), abnormal TSH or prolactin levels,
or any known metabolic or endocrinological disease. Women with
incomplete medical records were excluded from the study, as were women
who taking any medication.

The choice to use hCG trigger or urinary LH monitoring plus transvaginal
ultrasonography was made according to the patient's preference and
availability for monitoring. A home urinary ovulation prediction kit was
used to monitor urinary LH levels once a day, in the evening around
19:00 h, starting on cycle day 10. And serial ultrasonography for
follicular monitoring was also started on cycle day 10 for all cycles.
When ovulation was diagnosed, insemination was performed immediately.

In the spontaneous ovulation group (based on urinary LH monitoring and
transvaginal ultrasonography), insemination was carried out within 24
hours after detection of the first urinary LH positive test or upon
detection of ultrasound features suggestive of ovulation. In the induced
ovulation group (administration of hCG trigger), when a leading follicle
reached a diameter of 16 mm or urinary LH surge appeared, ovulation was
triggered using 10,000 IU of recombinant hCG (choriogonadotropin alfa,
Ovidrel(r); EMD Serono, Inc.). In our practice, the standard of care is to
perform two inseminations in a given cycle, approximately 24 hours and
36 hours after HCG injection \textsuperscript{13-15}; however, there are
clinical factors affecting the clinical decision to use single or double
IUI including patient demand, financial barriers, or ovulation time.

Frozen donor sperm were obtained from the Shandong Province Human Sperm
Bank of China, and were thawed on site on the day of insemination. All
sperm samples were prepared with a density gradient centrifugation
method using Puresperm TM (Nidacon, International
AB)\textsuperscript{16}. The quality of semen was evaluated before and
after processing (semen TMS).

The insemination procedure was the same for all women, bed rest was
maintained for 15 min after the insemination \textsuperscript{17}. A
urine pregnancy test was administered 14 days after insemination, and if
positive, a transvaginal ultrasound would be performed 14 days later to
assess the pregnancy outcome (including the number of gestational sacs,
viability, and location).

\textbf{Data Analyses}

Clinical pregnancies were confirmed by the presence of a fetal heartbeat
on ultrasound scanning 7 weeks after insemination. Miscarriage was
defined as loss of a clinical pregnancy before the 28th week of
gestation. Live birth was defined as delivery of a live neonate after 28
weeks' gestation. Our primary outcome measure was live birth rate. Our
secondary outcomes included clinical pregnancy rate and miscarriage
rate. In light of the significant differences detected related to
intrauterine insemination number between the hCG group and the urinary
LH groups , a subgroup analysis was performed to assess the impacts of
one vs. two inseminations in a given cycle for both the hCG and urinary
LH groups.

Statistical analysis was performed using SPSS Statistics 20.0 (IBM).
Mean values and standard deviations were calculated for each continuous
variable, whereas percentages were determined for the categorical
variables. Continuous variables were compared with Student's\emph{t}
-tests. Categorical variables were compared with chi-squared and
Fisher's exact tests. A single, multivariate logistic regression
analysis (incorporating ovulation timing method as a categorical
explanatory variable) was performed to assess the independent effect of
hCG administration on reproductive outcomes after adjustment for
possible confounding factors, including maternal age, BMI, number of
intrauterine insemination events, and basal hormone levels (FSH, LH,
estradiol, AMH). A \emph{P} value \textless{}0.05 was considered
statistically significant.

\textbf{Results}

A total of 5610 patients who were treated with IUI from January 2012
until December 2017 were included in the study. Despite the fact that
some women received several IUI treatments per fertility cycle, only
data for the first treatment (either single or double insemination) of
each woman was included in the analysis.

The baseline characteristics and hormonal profiles of the patients in
the hCG and spontaneous ovulation group are presented in Table 1. No
significant differences were observed regarding BMI, basal AMH, or
estradiol concentration between patients of the two groups, while slight
differences were detected in age and basal FSH and basal LH
concentrations.

Pregnancy outcomes are shown in Table 2. In crude analysis, compared to
the spontaneous ovulation group, the hCG group had significantly higher
rates of clinical pregnancy (27.40\% versus 22.73\%, OR (95\% CI): 1.28
(1.11--1.49); \emph{P} =0.001) and live birth rates (24.52\% versus
20.13\%, OR (95\% CI); 1.29 (1.11-1.50); \emph{P} =0.001). Additionally,
no difference in the rate of miscarriage was observed between the two
groups (10.50\% versus 11.46\%, OR (95\% CI): 0.91(0.60-1.36);\emph{P}
=0.671). Note that the significantly increased clinical pregnancy and
live birth rates of the hCG group were still detected after adjustment
for a number of confounding factors (Table 2).

To assess the effect of intrauterine insemination number on pregnancy
outcomes, a subgroup analysis (single IUI, double IUI) was performed
(Table 3, 4). Among women who received double IUI, there was no
difference between the hCG group and spontaneous ovulation group in the
rates of clinical pregnancy (27.30\% VS 25.00\%, OR (95\% CI): 1.12
(0.88--1.44); \emph{P} =0.343) or live birth (24.46\%VS20.66\%, OR (95\%
CI): 1.24 (0.96--1.62); \emph{P} =0.102). However, among single IUI
patients, the hCG group women achieved significantly higher rates of
clinical pregnancy (28.23\% versus 21.80\%, OR (95\% CI): 1.41
(1.09--1.81); \emph{P} =0.009) and live birth (25.00\% versus 19.91\%,
OR (95\% CI): 1.34 (1.03--1.74); \emph{P} =0.032).

\textbf{Discussion}

\textbf{Main Findings:}

In this study, we found that administration of hCG for triggering
ovulation was associated with increased pregnancy rates in IUI with
donor sperm in a natural menstrual cycle. When we divided the patients
into subgroups according to IUI number, the increased pregnancy rate in
the hCG group was only observed in the single IUI subgroup.

\textbf{Interpretation:}

Previous research has established that the success of IUI depends on
various factors, including maternal age, sperm quality, type of
subfertility, ovarian stimulation, and the timing of
insemination\textsuperscript{18, 19}.Given that spermatozoa and oocytes
have only limited survival times, the appropriate timing of IUI relative
to ovulation may be one of the most important factors influencing IUI
success \textsuperscript{6}. Ovulation typically occurs 25-56 h
following the onset of a spontaneous LH surge, whereas ovulation usually
occurs 36-48 h after hCG administration in natural cycles.

Administration of hCG makes clinical prediction of ovulation more
accurate; it permits planning for optimized time intervals between
ovulation and insemination possible \textsuperscript{20}. This increased
accuracy can likely help explain the significantly increased pregnancy
rates achieved by the hCG group women in the present study. When
insemination was performed twice, the window of sperm exposure to the
oocyte was significantly increased; this maybe help explain the similar
clinical pregnancy rates observed for the two
groups\textsuperscript{21}.

Several studies of ovarian hyperstimulation IUI cycles have demonstrated
beneficial effects of hCG administration on IUI
pregnancies\textsuperscript{22-24}. One study by Taerk \emph{et al.}
(2017) reported that hCG administration significantly increased clinical
pregnancy rates compared with monitoring of spontaneous serum LH surge
in subfertile patients undergoing controlled ovarian hyperstimulation
IUI cycles \textsuperscript{22}. Two additional retrospective studies of
stimulated IUI have also reported that higher pregnancy rates resulted
when hCG was given to trigger ovulation \textsuperscript{23, 24}.

Few studies have explored association(s) between hCG administration and
pregnancy outcomes in natural cycle IUI. Moreover, the few studies
addressing this topic have yielded inconsistent results. A Cochrane
meta-analysis by Cantineau \emph{et al.} (2014) reported no difference
in pregnancy rates or live birth rates between natural cycle IUI
patients timed according to spontaneous LH surge monitoring or hCG
triggering \textsuperscript{24}. However, note that these reports
included a total of only 264 women, and only one study reported live
birth rate data.

To date, only one randomized clinical trial has investigated the
pregnancy outcome of hCG administration for triggering ovulation in
natural cycle IUI \textsuperscript{9}. A total of 300 patients were
included in that study, of which 197 women used donor sperm. The trial
concluded that administration of hCG resulted in decreased ongoing
pregnancy rates. Given that the goal of IUI treatment is to achieve a
healthy live birth, it is unfortunate that live birth rate data for the
two groups was not reported from the trial.

A retrospective cohort study by El Hachem \emph{et al.} (2017) found no
difference in clinical pregnancy or live birth rates between urinary LH
monitoring vs hCG-triggered ovulation in natural unstimulated
therapeutic donor sperm insemination cycles \textsuperscript{11}. The
inclusion criteria of that study were strict: only normo-ovulatory women
were included. Notably, whereas the average age of the patients in that
study was 32, the mean age of patients in our study was 27 years. We
suspect that this 5 year age gap may be a major factor underlying the
inconsistent conclusions of the two studies.

\textbf{Strengths and Limitations:}

The current study had several strengths, the foremost of which was its
large cohort size. To the best of our knowledge, ours is the
largest-to-date study comparing the two major IUI timing methods for
natural cycle IUI. Moreover, our study monitored the live birth rate of
natural cycle IUI, data which has been reported rarely in previous
studies.

Limitations of our study include the use of urinary LH monitoring, which
has been associated with increased probability for false-negative
results; such results would cause inaccurate timing and thereby likely
contribute to decreased pregnancy rates \textsuperscript{3}. However,
considering its advantages over alternatives (like serum LH testing)
such as ease-of-use, non-invasiveness, and low cost, urinary LH
monitoring is widely used in the clinic \textsuperscript{26, 27}. It
also bears mention that our clinical pregnancy rate in the spontaneous
LH group was 22.73\%, a rate comparable to previously published natural
cycle IUI success rates. Second, our study is based on a retrospective
design. The inclusion criteria were strict, with only normo-ovulatory
women aged \selectlanguage{english}[?] 35 years who underwent IUI with high-quality donor sperm
included, which enabled analysis of a well-defined cohort of women with
no obvious confounding factors.

\textbf{Conclusion} :

In conclusion, the administration of hCG for triggering of ovulation is
associated with significantly higher pregnancy rates compared with
spontaneous ovulation in patients undergoing natural IUI. Thus, using
hCG for timing ovulation optimizes the chances of success for natural
cycle IUI with donor sperm.

\textbf{Acknowledgments}

We are grateful to Hong-bin Liu and Wei Zhou of Shandong Provincial
Hospital Affiliated to Shandong University for technical support. We
especially thank all the patients for participating in this study.

\textbf{Disclosure of interests}

The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

\textbf{Contribution to authorship}

Conceptualisation was by SM, W-ZJ and W-JP; data curation was by SY and
F-HR; formal analysis was by G-QQ, XJ, CW and W-ZJ; and writing was by
W-JP, W-ZJ and SM

\textbf{Details of ethics approval}

The Institutional Review Board, Shandong Provincial Hospital Affiliated
to Shandong University, Jinan, China, gave the ethical approval for the
study (Number 6166).

\selectlanguage{english}\textbf{Funding:}

The authors disclose receipt of the following financial support for the
research, authorship and/or publication of this article: this study was
supported by the Key Research and Development Program of Shandong
Province (2019GSF108090); the National Natural Science Foundation of
China (81801476); the Natural Science Foundation of Shandong Province
(ZR2019PH054, ZR2017BH046); the Medical and Health Science and
Technology Development Plan of Shandong Province (2016WS0411,
2016WS0404) and the Jinan Science and Technology Development Program
(201805026).

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\textbf{Table 1. Demographic characteristics of the patient population.}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
HCG administration\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
Spontaneous ovulation\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
\emph{P}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Patients, n\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4343\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1267\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Age (years)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
27.25\selectlanguage{ngerman}±3.40\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
27.51\selectlanguage{ngerman}±3.29\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.014\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
BMI (kg/m\textsuperscript{2})\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
22.11\selectlanguage{ngerman}± 3.15\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
22.14\selectlanguage{ngerman}± 3.19\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.864\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
AMH(ng/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.20\selectlanguage{ngerman}±2.90\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.28\selectlanguage{ngerman}±2.93\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.54\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
FSH(IU/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.64\selectlanguage{ngerman}±1.77\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.83\selectlanguage{ngerman}±1.82\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
LH (mIU/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.88\selectlanguage{ngerman}±2.39\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.07\selectlanguage{ngerman}±2.16\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.012\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Estradiol (pg/mL)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
34.75\selectlanguage{ngerman}±13.17\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
34.25\selectlanguage{ngerman}±12.69\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.617\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Endometrium thickness on the day of insemination (cm)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.01\selectlanguage{ngerman}±0.11\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.02\selectlanguage{ngerman}±0.14\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
IUI number\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.89\selectlanguage{ngerman}±0.31\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.29\selectlanguage{ngerman}±0.45\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as mean \selectlanguage{ngerman}± SD for continuous variables

BMI = body mass index; AMH = anti-Müllerian hormone; IUI = intrauterine
insemination.

\textbf{Table 2. Reproductive outcomes of the patient population.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Characteristics}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{HCG administration}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Spontaneous ovulation}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{AOR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{adj}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Clinical pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1059/3879 (27.30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
92/368 (25.00\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.343\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.356\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Miscarriage}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
110/1059 (10.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16/92 (17.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.55(0.31 0.99)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.52(0.29 0.94)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.039\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.029\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Live birth}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
949/3879 (24.46\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76/368 (20.66\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.24(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.25(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.102\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.103\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as n/n (\%) for dichotomous variables OR Odd ratio,
AOR adjusted odd ratio,

Clinical pregnancies were confirmed by the presence of a fetal heartbeat
on ultrasound scanning 7 weeks after insemination. Miscarriage was
defined as loss of a clinical pregnancy before the 28th week of
gestation. Live birth was defined as delivery of a live neonate after 28
weeks' gestation.

Analyses were adjusted for maternal age, BMI, number of intrauterine
insemination events, and basal hormone levels (FSH, LH, estradiol, AMH)

\textbf{Table 3. Reproductive outcomes of the single IUI group.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Characteristics}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{HCG administration}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Spontaneous ovulation}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{AOR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{adj}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Clinical pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1059/3879 (27.30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
92/368 (25.00\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.343\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.356\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Miscarriage}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
110/1059 (10.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16/92 (17.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.55(0.31 0.99)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.52(0.29 0.94)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.039\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.029\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Live birth}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
949/3879 (24.46\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76/368 (20.66\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.24(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.25(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.102\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.103\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as n/n (\%) for dichotomous variables OR Odd ratio,
AOR adjusted odd ratio,

Clinical pregnancies were confirmed by the presence of a fetal heartbeat
on ultrasound scanning 7 weeks after insemination. Miscarriage was
defined as loss of a clinical pregnancy before the 28th week of
gestation. Live birth was defined as delivery of a live neonate after 28
weeks' gestation.

Analyses were adjusted for maternal age, BMI, number of intrauterine
insemination events, and basal hormone levels (FSH, LH, estradiol, AMH)

\textbf{Table 4. Reproductive outcomes of the double IUI group.}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Characteristics}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{HCG administration}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{Spontaneous ovulation}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\textbf{AOR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{adj}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Clinical pregnancy}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1059/3879 (27.30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
92/368 (25.00\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.12(0.88 1.44)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.343\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.356\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Miscarriage}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
110/1059 (10.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16/92 (17.39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.55(0.31 0.99)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.52(0.29 0.94)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.039\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.029\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Live birth}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
949/3879 (24.46\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76/368 (20.66\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.24(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.25(0.96 1.62)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.102\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.103\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as n/n (\%) for dichotomous variables OR Odd ratio,
AOR adjusted odd ratio

Clinical pregnancies were confirmed by the presence of a fetal heartbeat
on ultrasound scanning 7 weeks after insemination. Miscarriage was
defined as loss of a clinical pregnancy before the 28th week of
gestation. Live birth was defined as delivery of a live neonate after 28
weeks' gestation.

Analyses were adjusted for maternal age, BMI, number of intrauterine
insemination events, and basal hormone levels (FSH, LH, estradiol, AMH)

\selectlanguage{english}
\FloatBarrier
\end{document}

