Spontaneous pregnancies and determinant factors in infertility: A cross-sectional study

Abstract Background The phenomenon of infertility may be derived from different factors - either in males or females or both genders, including few unexplained factors. It is generally managed by medical and surgical treatments. Objective To find a relation of occurrence of spontaneous pregnancy (SP) with effective factors in infertility. Materials and Methods This cross-sectional study was conducted at two referral infertility centers (university and privacy center) in the southwest of Iran from March 2015 and March 2016 on 655 infertile couples, who were divided in two groups of with (n = 31) and without (n = 624) SP. The variables included female and male age, male smoking, male job, the place of living, the causes of infertility, the type and duration of infertility, and the subgroups of infertility causes. Results Infertility may be caused due to both male- and female- related factors (47.5%). While female-related infertility was found in 31.5%, male-related infertility in 14.5%, and infertility due to unexplained factors in 6.6% of our patients. The rate of SP was 4.7%, which had a significant relation with the duration of infertility (p = 0.01), with women's age (p = 0.048), unexplained infertility (p = 0.001), and husband's job (p = 0.004). Conclusion The occurrence of SP in infertile couples was related to age of the female partner, the duration of unexplained infertility, and the male partner's job.


Introduction
Today, infertility is considered as one of the most pertinent public health concerns in all human societies. Based on recent studies by WHO, approximately 8-10% of couples somehow face fertility-related problems, which means that about 50-70 million couples are facing this problem worldwide (1,2). Several factors can cause infertility in couples including biological, physiological, environmental, or acquired factors.
The infertility treatment is generally based on the cause of infertility; however, some infertile couples do not follow-up their treatment properly (3). A follow-up of Iranian and Turkish infertile patients after an ART failure showed that Iranian patients ceased the treatment more than the Turkish. The reasons reported were economic problem, hopelessness, distress of drug side effect, achieving pregnancy, child adoption, lack of spouse partnership and divorce. Nevertheless, the rate of spontaneous pregnancy (SP) was significantly higher in Iran than in Turkey. There was a correlation between the duration of infertility and female factor infertility with SP (4).
The aim of this study was therefore to find a correlation of SP determinant factors in infertility in Ahvaz, Iran.

Ethical consideration
This study was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences. Informed consent was obtained from all couples for the use of their data. Additionally, t test and Chi-square test were respectively used to compare the quantitative and qualitative variables between groups. The conventional p-value of ≤ 0.05 was considered as an overall significant level.

Results
Six hundred fifty-five infertile couples participated in the study. The SP occurred in 31 (4.7%) during the study period (Table I).
Frequency of the causes of infertility was defined in Table I.

Discussion
In the study, the rate of SP was reported to be 4.7%. Frequency the occurrence of SP in order to the causes of infertile subgroups was combined, unexplained, female and male factor, respectively. So, it showed the rate of SP in subgroup unexplained infertility was more than the other subgroups. There was no statistically significant relationship between primary and secondary infertility with SP, however, the duration of infertility for ≤ 3 years was associated with a significant increase in the rate of SP. Also, the mean female age was significantly lower in women with SP. The type of male's job was also significantly related to the SP.
The limitation of diagnostic procedure for predicting pregnancy is well-known, for example, a study exploring pregnancy rate after hystersalpingo-contrast sonography showed that when two tubes were closed, the pregnancy rate was reduced to 15.04%, so the occlusion of both the tubes have a false positive result. In this study, a univariate analysis showed that younger age was positively related to initiation of pregnancy as found in our study; however, the infertility type, duration of menstrual cycle, dysmenorrhea, and parity were unrelated to pregnancy (7). Another study showed that some patients with premature ovarian insufficiency have an intermittently ovarian activity with an overall 5% probability of pregnancy (8). In addition, we know that the current WHO criteria for semen quality do not distinguish between fertile and sub-fertile (9). So, we could expect an occurrence of SP despite the results of para-clinic.
Further, a study was conducted to determine the reasons and incidence for withdrawal from a waiting list for IVF. It was reported that about 13% of the patients gave up before going through their first IVF cycle and 37% of them has an SP, which is the same rate of SP as reported in our study. Most of the pregnancies occurred within three months after the patient had been set up for a waitlist, which suggests that psychological factors might be effective (10). As in our study, they showed that we should give hope, especially to young couples with unexplained infertility, although they might have to wait for a long time. They also reported that SPs mostly occurred in 2-4 years of successful or unsuccessful IVF attempts (11). Similar to our findings, another study determined that the younger women and also shorter duration of infertility had higher rate of spontaneous pregnancy after surgery (12). Another study showed that SP occurred after the management of autoimmune disorders (13).
Moreover, the initial experimental management for six-month results were reported in couples with unexplained sub-fertility and that an intermediate prognosis of natural conception is effective (3,14). We also know that female age has a prominent negative impact on fertility and the solutions are not simple, however, an alternative like validated dynamic models could predict both natural and ART-mediated in short time (15). Another study showed that allostatic load that is specific in chronic situation like infertility was not associated with fertility outcomes like conception, spontaneous abortion, and live birth (16). However, a cohort study on 4,999 couples showed that the prediction ranges could help in counselling couples for at least two years after their fertility work-up (17). Additionally, a longitudinal cohort study showed a 71.6% live birth after ART and 28% after SPs or both up to five years (18). The small rate of SP in our study might have been affected by the environment, especially heat intensity, genetics, socioeconomic factors, nutrition, and obesity. On the other hand, many studies have been conducted for increasing fertility, for example, in a randomized controlled trial, the effect of endometrial scratching was conducted in couples with unexplained infertility and a good prognosis, and we must wait for their results (19).
In addition, several articles have pointed the lifestyle factors such as diet, use of fish consumption, exercise, intervention for losing weight, and optimized counseling associated with the SP and IVF success rate (20). Obesity affects SP in sub-fertile ovulatory women, so it needs to be managed (9). While, the limitations of this study were its retrospective pattern and short follow-up, the strength of the study was the evaluations of SP infertile people from a specific geographical region and the number of participants in the study; therefore, we suggest a multi-centric research. In addition, we can expect to achieve an SP despite