Relationship between the Time of Intrauterine Insemination and Pregnancy Outcome, Based on Islamic Recommendations

Introduction he population growth rate in Iran has been reduced to 1.24% which has recently attracted the attention of the country's authorities (1). Despite widespread family planning policies in recent years, couples are less reluctant to have more than one child. Moreover, infertile couples have to pay a large sum of money to infertility treatment centers and even if they succeed to become pregnant, there is still a risk of T Abstract


Relationship between the Time of Intrauterine Insemination and Pregnancy Outcome, Based on Islamic Recommendations
Introduction he population growth rate in Iran has been reduced to 1.24% which has recently attracted the attention of the country's authorities (1). Despite widespread family planning policies in recent years, couples are less reluctant to have more than one child. Moreover, infertile couples have to pay a large sum of money to infertility treatment centers and even if they succeed to become pregnant, there is still a risk of pregnancy loss or congenital anomalies in the neonate for a variety of reasons (2). Depression and anxiety following the loss of pregnancy (3.4) and the expenditure of significant amounts of time and money are the challenges facing many couples. A normal pregnancy is expected to result in the birth of a healthy neonate with the proper weight. However, there is always the possibility of premature birth, low birth weight, birth defects, infant death, and abortion (5). According to previous studies, there are various reasons for the loss of the pregnancy, such as endocrine causes (e.g., luteal phase defects (6), diabetes (7), hypothyroidism (8), and polycystic ovaries (9)), infectious causes (10), anatomical defects of the uterus (11), environmental causes (e.g., smoking (12), alcohol consumption (13), air pollution (14), and excessive coffee consumption (15)), and old age of parents (4,16,17). In infertility centers, only the medically known factors are considered and examined in infertile couples and in many cases, despite the elimination of all barriers to fertility and the use of pharmacological and invasive methods, the success rate of fertility is still very low. The Center for Disease Control and Prevention has reported the success rate of intrauterine insemination (IUI) to be 4-9% and in vitro fertilization in those below 35 years old and over 35 years old to be 31-46%, and 13%, respectively (18). However, the cause of many early abortions, genetic disorders, or other adverse outcomes is still unknown (19) and requires extensive research.
In the searches conducted in the database of articles and dissertations in the field of medicine and seminary education, no domestic or foreign study was found about the factors affecting the pregnancy outcome with an Islamic approach. On the other hand, in valid Islamic sources, such as Man La Yahduruhu al-Faqih (20), al-Kafi (21), and Wasa'il al-Shia (22), there are many narrations about the time of fertilization and its effect on the physical, mental, and spiritual health of the infant at the time of birth and even later years. For example, according to a quotation by Imam Sadiq (PBUH), fertilization at the beginning, middle, and end of the lunar month is one of the factors that lead to physical deficiency and abortion (20). Moreover, the Prophet Muhammad (PBUH) who considered characteristics, such as eloquence, intelligence, and wit as the signs of spiritual health (23), has pointed out the effect of the time of fertilization on the child's spiritual health. Furthermore, he has said that the result of sexual intercourse on Friday night is the birth of an orator and eloquent child (22). Given the valuable treasure of the Ahl al-Bayt's recommendations on various aspects of life, as well as the limited and incomplete nature of the experimental sciences, the researchers hope that by relying on the advice of the Infallibles, they will be able to improve the pregnancy outcomes and facilitate the birth of healthy children with the best physical, psychological, and spiritual characteristics. Therefore, the present study was conducted to determine the relationship between the time of IUI and the pregnancy outcome based on Islamic narrations.

Methods
The present historical cohort (descriptiveanalytical) study was conducted in the infertility center affiliated with the Academic Center for Education, Culture, and Research in Qom province, Iran. The study population was the couples who referred to this infertility center during 2011-15, underwent sex selection IUI procedure through the Erickson method, and consumed folic acid according to the instructions. The eligible couples were enrolled in the study using the census sampling method. The exclusion criteria were 1) repeated abortions, 2) primary infertility, 3) poor sperm quality and quantity, 4) anatomical abnormalities of the uterus, 5) endocrine and autoimmune disorders, and 6) untreated genital infections.
In total, out of the 325 existing medical records, 298 couples met the inclusion criteria. It should be noted that all the studied couples were under the supervision of an urologist and had the minimum quality and quantity required for sperm to undergo IUI.
The data were collected through a checklist which included variables, such as the age, education level, occupation, and nationality of the spouses, as well as cousin marriage or not, marriage duration, gravidity, previous pregnancy outcome, history of secondary infertility, smoking, time of IUI (disapproved, recommended, and neutral times), pregnancy test result, pregnancy outcome (if the pregnancy test is positive), and the gender of the fetus. It should be noted that in this study, the unhealthy pregnancy outcome includes abortion, ectopic pregnancy, premature birth, and neonatal abnormalities. In this study, the medical record of the couples who underwent sex selection IUI procedure was reviewed and the time of IUI was compared with the Islamic recommendations. Therefore, the records were divided into three groups. The first group was those whose IUI was performed during the Islamic makruh (disapproved) time including the time when the moon is in Scorpio or in shadow (20,22,(24)(25)(26) [when the moon is in the Scorpio or in front of the constellation Scorpio, which happens about 4 days per month and is calculated according to accurate astronomical calculations] (27), at the beginning, middle, and the end of the lunar month (20-22, 24-25, 27), in the afternoon and on the nights of Eid al-Fitr, Eid al-Adha, and Mid-Sha'ban, the time between the false dawn and true dawn, between the adhan and iqama, at the time of natural disasters (22,24 (22,24).
Finally, the third group consisted of those whose IUI procedure was performed during mubah (neutral) times (without mentioning whether it is recommended or not in Islamic traditions). Finally, during the telephone interview, the results of the IUI procedure, including positive and negative pregnancy tests, and, if positive, the pregnancy outcome were determined and the checklist was completed.
The collected data were analyzed in the SPSS software (version 20). Moreover, the Kolmogorov-Smirnov test was used to check the normality of quantitative variables. Furthermore, the research hypotheses were also analyzed using the chi-square, Fisher's Exact, and Mann-Whitney U tests.
Regarding the confidentiality of the data, a code was assigned to each record file which was also put on the questionnaire and the data collection sheets. Moreover, this research was approved by the Regional Ethics Committee of Qom University of Medical Sciences, Iran (registration code IR.MUQ.REC.1396.27).

Result
In this study, out of the 298 couples, the pregnancy test of 54 couples was positive. In couples with positive pregnancy test results, the mean and standard deviation of the age of men and women were 37.9±3.5(32-46), and 32.2±3.8 (24-39) years. It was found that the age of the father (P=0.48) and mother (P=0.80) had no significant relationship with the pregnancy outcome. The demographic characteristics of the study subjects are shown in Table 1 based on the pregnancy outcome.
Furthermore, the Kolmogorov-Smirnov test results revealed no significant difference between the distribution of marriage duration with the normal distribution (P=0.51). Therefore, the independent t-test was used to investigate the relationship between pregnancy outcome and marriage duration. Based on the results of this test, the mean values of marriage duration in the two groups did not have a significant difference (P=0.87).
The results of the Kolmogorov-Smirnov test showed a significant difference between the distribution of the gravidity with the normal distribution (P<0.0001). Therefore, the Mann-Whitney U test was used to investigate the relationship between the pregnancy outcome and the number of pregnancies; however, no significant relationship was found (P=0.88).
The findings of this study revealed a significant difference between the three groups in terms of positive pregnancy test results (P=0.003). Moreover, a significant relationship was found between the time of IUI performance and the pregnancy outcome (in 298 couples) (P=0.023) so that the highest number of healthy births (20%) was observed in those who underwent IUI procedure at the recommended times ( Table 2).
Out of 54 couples with a positive pregnancy disapproved time (64%), respectively. Moreover, based on the time of IUI, the highest and lowest frequency of abortions were found in the disapproved time, especially the time of the moon in Scorpio (25%), and the recommended time, especially on Thursday noon, respectively. However, no significant relationship was found between the time of IUI (recommended, disapproved, and neutral) and the pregnancy outcome (healthy and unhealthy) (Table 3).
Furthermore, no significant relationship was

Discussion
The present study was the first research that investigated the relationship between IUI time and its results according to Islamic traditions. In this study which was performed on a statistical population of 298 couples, the most important finding was that there is a significant relationship between the time of IUI performance and its outcome. For this purpose, the number of IUI cases that resulted in pregnancy and finally the birth of a healthy infant were compared to the number of IUI cases whose results were negative or even if they were positive, did not lead to the birth of a healthy neonate. Eventually, it was found that insemination at the recommended time resulted in the highest number of birth of healthy neonates.
Investigation of the studied pregnant women (54 subjects) revealed no significant relationship between the time of IUI performance and pregnancy result (P=0. 19), which could be due to the small sample size (54 couples). However, the comparison of the obtained percentages indicated a significant difference between the groups with recommended and disapproved times, regarding the birth of healthy or unhealthy neonates, the rate of abortion, and ectopic pregnancy. In this regard, 92.3% of all the pregnancies which were the result of insemination at the recommended time resulted in the birth of a healthy child, while the lowest rate belonged to those that happened at the disapproved time (64%). In other words, 36% of pregnancies that were conceived at disapproved times led to problems, such as abortion, premature birth, ectopic pregnancy, or neonatal abnormality. Nevertheless, the rate of such issues was only 7.7% in pregnancies that were conceived at the recommended time. These findings are in line with the quotes of the Infallibles since many of them have discouraged fertilization at the beginning, middle, and end of the lunar month, afternoons, when the moon is in Scorpio and in shadow (when the moon is in the Scorpio or in front of the Scorpio constellation which happens about 4 days per month and is calculated through accurate astronomical calculations). They also have referred to negative physical, mental, and spiritual consequences for pregnancies that are conceived during these times. Some of them have even have considered them as disapproved in general. For example, Al-Hurr al-Amili quotes from Imam Sadiq (PBUH) in Wasa'il al-Shia that: "Fertilization, when the moon is in Scorpio, causes the humans not to see what they want and what is good for them" and he continues that in another narration Imam Sadiq (PBUH) says: "If intercourse during this time results in conceiving a child, it will be aborted before the pregnancy is complete" (22). In another narration from Imam Musa al-Kadhim (PBUH), it is stated that "Intercourse during this time will put the conceived child at the risk of abortion before the pregnancy is finished" (21). Moreover, according to Imam Sadiq (PBUH) narration, sexual intercourse at the beginning, middle, and end of the lunar month causes the abortion of the conceived child and if a child is born, it will have mental or physical disorders (20).
In this study, more than half of the abortions (55%) happened to inseminations were done at disapproved times, especially when the moon was in Scorpio, which is consistent with the recommendations of the Infallibles (21,22). However, the rate of abortion at the recommended time was only 11%.
Furthermore, in the present study, the highest number of healthy newborns (92.3%) was related to insemination at the recommended times, especially during April, May, and February, which is consistent with a quotation from Imam Reza (PBUH) which is: "Astronomical positions affect the practice of sexual intercourse and it is better to have intercourse on the nights when the moon is in the Aries (April) or Aquarius (February). Even better than these two is Taurus (May), which is the Sharaf Qamar (when the moon is in its strongest form). When the moon is in Taurus, it strengthens the zygote into embryo in the uterus" (28).
In the present study, no significant relationship was found between the pregnancy outcome and parental age which is agreed with a study performed by Hurley EG and DeFranco EA which found that the increase of the paternal age did not lead to a significant increase in the rate of preeclampsia, preterm delivery, fetal growth restriction, congenital anomaly, genetic disorder, or hospitalization in the neonatal intensive care unit (29). However, in a study conducted by Riffat J et al., if the age of the father was more than 35, it was associated with an increased risk of abortion (16).Furthermore, a study carried out by Khalil A et al. found that the risk of abortion, preeclampsia, diabetes, and low birth weight increased with the increase of maternal age (5). The results of these two studies are inconsistent with those of the present study. This inconsistency could be due to different statistical populations and the age of parents in this study. Since in the present research, the mean of the paternal age was about 38 years old and the mean of the maternal age was 33 years old; therefore, the majority of the participants were below 35 years old.
In this study, no significant relationship was found between smoking and drug use with pregnancy outcomes. However, the results of a study conducted by Wang L, Yang Y, Liu F et al. indicated that parental smoking was associated with abortion (12), and thereby are inconsistent with those of this study.
In the present study, the desired gender of the newborn coincided with the actual gender of the neonate in 62.5% of the cases. Moreover, the overall rate of abortion was 16.6% while this rate at disapproved and recommended times was 20% and 7.7% respectively. Nevertheless, in a study performed by Khalili et al., more than 70% of cases gave birth to their desired child and the rate of abortion was 12.5% (30).
As a limitation of this study, it is mentioned that in Islamic narrations, various times of day and month have been described as disapproved and recommended. For instance, nights of Monday, Tuesdays, Thursdays, Fridays, and during and after Friday evenings have been declared as recommended times. In addition, Wednesday nights, Mid-Sha'ban, Eid al-Fitr, and Eid al-Adha have been declared as disapproved. However, due to the working hours of infertility centers which are from morning till evening, official holidays, such as Fridays, Eid al-Fitr, and Eid al-Adha, many instances mentioned in quotations cannot be investigated and only a limited number of disapproved and recommended times can be studied. Therefore, it is suggested that more extensive studies be conducted by the conduction of night shifts and the performance of IUI procedures at night so that all the disapproved and recommended times can be thoroughly examined.

Conclusion
According to results, the time of IUI had a significant effect on the health of the infant. Therefore, the right time for the IUI should be emphasized and the results be evaluated in future studies. Moreover, the couples who are planning to become pregnant should be advised to avoid intercourse during disapproved times and choose the recommended times for conceiving to achieve the desired results and give birth to a healthy child. Furthermore, children who were conceived at recommended times are hoped to have certain positive moral characteristics, such as eloquence, wisdom, satisfaction with God's will, and memorization of the Quran. The result of conceiving at the disapproved times may lead to the birth of a child with unpleasant characteristics such as wickedness, cruelty, bloodthirstiness, and stinginess. The determination of these matters requires a prospective study within a span of several years. Such a study will be very valuable and necessary since if such a relationship is significant, one can hope for a better outcome by adherence to religious orders.