Pregnancy outcomes with undescended testis husbands: influenced by wive’s life style and surgical correction before 1 year

Background The most prevalent sexual differentiation disorder in males is undescended testis (UDT), which occurs when the testis is absent from the scrotum or cannot be brought down during a physical examination. Pregnancy outcome may be influenced by the wife’s lifestyle and surgical correction within the past year 
Objectives This study aims to determine pregnancy outcome in Assisted Reproductive Technology (ART) on a wive with a UDT husband assessed by the wive’s life style and surgery correction before 1 year. 
Methods A cross-sectional study was conducted. Data were taken from patients who underwent Assisted Reproductive Technology at AMC Hospital, Yogyakarta. Data collection from 2018 to 2021. Samples in the unilateral and bilateral groups were 20 husbands. Wilcoxon Signed Rank Test helped carry out the analyses. 
Results There was an association between infertility and UDT either unilaterally or bilaterally (p = 0.009). Most UDT husbands had a BMI in the overweight category and the average age was 28 and 29. Other factors such as the wive’s life style and surgery correction before 1 year , including smoking habit, alcohol consumption, addictive drug and hormonal drug, had no significant effect on the success of pregnancy outcome (p > 0.05). 
Conclusions Although pregnancy outcome in unilateral and bilateral UDT patients was not statistically significant, clinically, the pregnancy outcome was better in husbands with unilateral UDT by IUI than in IVF. 
Bangladesh Journal of Medical Science Vol. 23 No. 02 April’24 Page : 455-462


INTRODUCTION
The most common disruption of male sexual differentiation is cryptorchidism, which occurs when the testis is absent from the scrotum or cannot be brought down during a physical examination. 1,2,31-4% of full-term and up to 45% of preterm male newborns are affected by cryptorchidism, also known as UDT. 2 UDT is classified into 2 types : unilateral and bilateral. 3,4Unilateral UDT occurs four times as frequently as bilateral UDT 3 .The condition potentially compromises gonadal function. 2,3,4

Background
The most prevalent sexual differentiation disorder in males is undescended testis (UDT), which occurs when the testis is absent from the scrotum or cannot be brought down during a physical examination.Pregnancy outcome may be influenced by the wife's lifestyle and surgical correction within the past year Therefore, early detection of UDT between the ages of 6 and 12 months is crucial for reducing germ cell loss and enhancing the fertility index of an individual. 1 Both gonocyte transformation into Ad spermatogonia and programmed germ cell death are impeded by undescended testes. 2,3After puberty, abnormal sperm counts are associated with a defect in gonocyte transformation into Ad spermatogonia. 2,3UDT affects about 10% of infertile men. 3 Even though they have a lower fertility rate, men who have undergone unilateral UDT have the same paternity rate as the general population. 2,3Bilateral UDT patients have lower fertility and paternity chances. 3Adults with bilateral UDT are more likely to be infertile. 1,2,3,4fertility is defined as the inability to conceive after twelve months of unprotected sexual contact. 5The UDT husband is predisposed to infertility and testicular cancer. 1,4UDT is linked to an high risk of infertility and poor sperm quality in the future. 6In order to prevent infertility, surgical correction of undescended testes should be performed prior to the age of one year. 7ssisted Technology Reproductive is another method for enhancing paternity.IUI and IVF are two types of Assisted Reproductive Technologies (ART) that can assist infertile couples in achieving pregnancy. 8,9,10.IUI is a common method for treating infertility caused by unknown factors and male infertility (certain sperm disorders).It can also be used to treat infertility and sexual dysfunction caused by problems with cervical mucus. 8An IVF cycle typically begins with ovarian stimulation, followed by the retrieval of multiple mature oocytes that have been fertilized in the laboratory to create embryos. 8,11Assisted reproductive technology encompasses a variety of clinical treatments and laboratory procedures, including the in vitro manipulation of human oocytes, ovarian tissue, sperm, testicular tissue, or embryos with the aim of establishing a pregnancy immediately. 10th the husband and wife have an impact on the success of a pregnancy.A lifestyle is one factor that affects the wife's fertility. 12As BMI rises, the negative effects of smoking and alcohol consumption on fecundity and gestational age intensify. 13,14Recent observational and experimental studies have demonstrated that a healthy lifestyle improves the general health and IUI and IVF success rate of infertile patients. 12The lifestyle of the mother prior to conception has a substantial effect on gamete function, early placentation, and embryo development. 14Depending on their reproductive ambitions, many women require effective assisted reproductive technology. 13,15Uncertainty persists regarding the factors influencing ART success and the most effective method for achieving pregnancy. 16ouples with UDT husbands require emotional support in addition to a healthy lifestyle in order to mitigate the effects of anxiety and depressive disorders. 17Therefore, this study aims to determine pregnancy outcome in ART on a wive with a UDT husband assessed by the wive's life style and surgical correction before 1 year.

METHODS
This research is non-experimental with a cross-sectional study.Data were taken from patients who underwent the Assisted Reproductive Technology (ART) process at the Obstetrics and Gynecology Clinic, Asri Medical Center Hospital (AMC), Yogyakarta.Data collection from 2018 to 2021.The data collection technique was total sampling with 20 Unilateral UDT husbands and 20 Bilateral UDT husbands.The inclusion criteria for this research were women who performed Assisted Reproductive Technology (IUI/IVF) at Asri Medical Center (AMC) Hospital, Yogyakarta with UDT (Unilateral/ Bilateral) husbands.The exclusion criteria for this study were women who performed Assisted Technology Reproductive (IUI/IVF) with their husbands UDT (Unilateral/ Bilateral) but their husbands refused to be respondents.
The data collection method used a checklist to assess the wive's life style, while the correction before 1 year and pregnancy outcome data were taken from the medical record.The wive's life style variable was categorized into "Yes" and "No".The smoking habit variable was active smokers, while the hormonal drug consumption variable was females who received oral hormone therapy and contraception.The dependent variable in this study was the result of Assisted Reproductive Technology (ART), namely IUI and IVF.Respondents in this study were given prior informed consent for the approval of data collection.The results of this study were carried out by SPSS data with Wilcoxon Signed Rank Test analysis.This analysis determined pregnancy outcome in ART on wive's with UDT husbands assessed by the Available at: http://www.banglajol.info/index.php/BJMSwives' life style and surgery correction before 1 year.
The studies involving human respondents were reviewed and approved by Gadjah Mada University (KE/FK/0783/EC/2021).

ETHICAL CLEARANCE
This research involving human participants were reviewed and approved by Gadjah Mada University (KE/FK/0783/EC/2021). Written informed consent for respondents was required for this research following the national legislation and the institutional requirements

RESULTS
According to Table 1, the mean BMI of unilateral and bilateral UDT husbands is 25.78 and 25.75, respectively.The mean BMI falls under the category of overweight.On the basis of age group characteristics, there was no significant difference between the two age groups (p = 0.083), with mean ages of 28 and 29 years, respectively.With respective p values of 0.78 and 0.562, there was no statistically significant difference between smoking and alcohol consumption.Moreover, infertility characteristics (p = 0.009) were significantly associated with undescended testis (UDT).Bilateral UDT resulted in a higher rate of infertility than unilateral UDT.Table 2 shows that twenty UDT husbands (unilateral and bilateral) involved in this study performed Assisted Technology Reproductive (IUI/IVF).The study results were positive (pregnant) and negative (not pregnant).
The results showed that most of UDT husbands had more positive pregnancy outcomes with the IUI method than IVF consecutively with IUI n = 14 (70%), and n bilateral = 15 (75%).Whereas in IVF unilateral n = 11 (55%), bilateral n = 14 (70%).Based on table 2, the p-value of UDT (unilateral = 0.439 and bilateral = 0.763).Thus, there was insignificant difference in pregnancy outcomes between unilateral and bilateral UDT husbands who performed IUI and IVF.Table 3 shows that the wive's lifestyle is divided into smoking habits, alcohol consumption, addictive drugs, and hormonal drugs.The results are either positive (pregnant) and negative (not pregnant).The first is the smoking habit.Compared to those who did not have a smoking in unilateral and bilateral UDT husbands, wives who had a smoking habit showed more negative pregnancy outcomes than positive results.In unilateral UDT there was a negative pregnancy outcome, namely wives with smoking habits 3 (15%) and wives who did not smoke 11 (55%).Meanwhile, in bilateral UDT, 9 (45%) wives had smoking habits and 9 (45%).In addition, unilateral UDT (p = 0.573) and bilateral UDT (p = 1.00) did not have a significant relationship with smoking habit.
The second is alcohol consumption.The wives who consumed alcohol compared to those who did not consume alcohol showed more negative pregnancy outcomes than positive results.In unilateral UDT there was a negative pregnancy outcome : wive with 1 (5%) alcohol consumption and 13 (65%).Meanwhile, in bilateral UDT, wives who consumed alcohol were 1 (5%), and mothers who did not consume alcohol were 17 (85%).In addition, unilateral UDT (p = 0.502) and bilateral UDT (p = 0.732) did not have a significant relationship with alcohol consumption.
The third is addictive drugs.None of the wives consumed addictive drugs.The majority of wives who did not use addictive drugs showed more negative results on pregnancy outcomes, namely n unilateral = 14 (70%) and n bilateral = 18 (90%) compared with positive results, namely n unilateral = 6 (30%) and n bilateral = 2 (10 %).The addictive drug factor had no p-value because none of the respondents used addictive drugs.
The last is hormonal drugs.Wives who consumed hormonal drugs compared to those who did not take hormonal drugs showed more negative pregnancy outcomes than positive results.In unilateral UDT, there was a negative pregnancy outcome, seven wives took hormonal drugs (35%) and equally, 7 wives did not take hormonal drugs (35%).Meanwhile in bilateral UDT, 15 (75%) wives consumed hormonal drugs, and 3 did not (15%).In addition, unilateral UDT (p = 0.492) and bilateral UDT (p = 0.531) did not have a significant relationship with hormonal drugs.Table 4 shows the relationship of surgical correction before 1 year to pregnancy outcome.The majority of husbands who did not have surgery correction before 1 year showed more negative results on pregnancy outcomes, including n unilateral = 13 (65%), and bilateral n = 15 (75%) compared to positive results n unilateral = 4 (20%) and n bilateral = 1 (5%).In addition, unilateral UDT (p = 0.133) and bilateral UDT (p = 0.264) had no significant association with surgery correction before 1 year.

DISCUSSION
To investigate pregnancy outcome in ART on wive's with UDT husbands assessed from their life style and surgery correction before 1 year.

Characteristics of UDT Husbands
This study found that the mean BMI in UDT husbands included the overweight category.Obesity has a negative impact on the development of the penis and testicles. 18There is a correlation between paternal obesity and a decline in male fertility.Due to higher DNA fragmentation levels, abnormal morphology, and low mitochondrial membrane potential in their sperm, obese men are more likely to be infertile. 19Another study found that men with a BMI greater than 25.0 kg/ m2 had a lower IVF pregnancy rate. 20Obesity hinders the fertility of not only men but also women.A study stated that obesity is related to hyperandrogenism, hyperinsulinemia, insulin resistance, and metabolic syndrome in infertile women. 21This study found that the majority of UDT husbands were between the ages of 20 and 30, with a mean age of 28 years for unilateral and 29 years for bilateral procedures.Age at diagnosis is an important prognostic factor for undescended testes because the risk of developing testicular cancer and infertility rises with age. 19,22me of UDT's husbands are smokers and alcoholics.Male smokers had more methylation changes in their sperm DNA than nonsmokers, according to a study. 19nother study stated that teratozoospermia was found in 72% of men who drank >80 g/day and 63% of men who drank moderately (40-80 g/day). 22Undescending testes were also associated with infertility, according to the findings.Bilateral UDT was associated with a higher rate of infertility compared to unilateral UDT.In addition, men with bilateral UDT had significantly lower paternity rates than men with unilateral UDT and those without UDT. 23Men with bilateral UDT are three-and-a-half times more likely to be infertile than men with unilateral UDT.After one year, the incidence of azoospermia in untreated undescended testes ranges from 13% to 89% in unilateral and bilateral cases. 2,4,19,24ta of frequency pregnancy outcomes UDT (Unilateral/ Bilateral) husbands on performed ART (IUI/IVF) Men with bilateral UDT had significantly lower paternity rates than men with unilateral UDT and those without UDT.Men with bilateral UDT are threeand-a-half times more likely to be infertile than men with unilateral UDT.After one year, the incidence of azoospermia in untreated undescended testes ranges from 13% to 89% in unilateral and bilateral cases. 1,2,3,19early 10% of men with fertility problems have a history of UDT and orchidopexy, 20-27% of adult men acquire azoospermia, and 3-8% have oligo-teratoasthenospermia previously identified with male descent testes; all of these conditions are associated with high rates of male infertility. 19Twenty UDT husbands used the ART method, including IUI and IVF.This study did not show a significant difference in pregnancy outcomes between unilateral and bilateral UDT husbands who performed IUI and IVF.This finding could be due to the limited study sample.The weakness of this study lies in the small number of samples because the participants were only selected from one reproductive clinic.
However, the majority of UDT (Unilateral and Bilateral) husbands who achieved a successful pregnancy utilized IUI rather than IVF.Intrauterine insemination (IUI) and in vitro fertilization (IVF) are two Assisted Reproductive Technologies (ART) that may help infertile couples conceive. 8,9,25Treatment with IUI in a stimulated cycle can result in a higher cumulative pregnancy rate than to other treatments. 22The majority of husbands with unilateral UDT were more likely to have a successful pregnancy than those with bilateral UDT.Even after surgical correction, the prevalence of cryptorchidism can reach 32%, and nearly double in bilateral UDT.89% of patients with bilateral cryptorchidism who are left untreated will develop azoospermia. 3,23,24.
Data of pregnancy outcome in UDT Husband (Unilateral/Bilateral) correlated with the wive's life style

Smoking habit in pregnancy outcome
Some studies have reported that smoking harms the ability to conceive for both men and women. 25The negative effects of smoking before and during pregnancy include infertility, ectopic pregnancy, low birth weight, and preterm delivery. 18,26This study showed that in wives who smoked and did not smoke, there was no significant difference in pregnancy outcomes, as evidenced by the majority of negative pregnancy outcomes.Due to the primary influencing factor, which was the husband's UDT.Men with a history of unilateral UDT, however, have a lower fertility rate. 2 Compared to non-smoking partners, smoking in women is associated with delayed conception, lower clinical pregnancy, and an increased rate of spontaneous miscarriage in both naturally conceived couples and those undergoing in vitro fertilization (IVF) techniques. 18,25,26Thus, women should be advised to stop smoking before they try to conceive. 8,18Diet, physical activity, psychological stress, socioeconomic factors, BMI, smoking, alcohol, caffeine, and psychoactive substances all impact pregnancy success. 14,27

Alcohol consumption in pregnancy outcome
Alcohol use has an impact on women's health. 12,23,24his study showed that wives who consumed alcohol and did not consume alcohol had no significant difference in pregnancy outcomes, as evidenced by the majority of negative pregnancy outcomes.Due to the primary cause, which was the husband's UDT experience.In addition, it was affected by the lack of research samples, and the fact that the majority of participants did not drink alcohol.The effects of alcohol on endogenous hormone levels and embryo quality have been linked to lowered fertility and conception. 24buse and consumption of alcohol during pregnancy has been linked to miscarriage, stillbirth, and fetal alcohol spectrum disorder. 23

Addictive drugs in pregnancy outcome
Observational studies found that addictive drug use before and during pregnancy endangers fetal development and has implications for women's reproductive function and fertility. 24This study showed that none of the wives used addictive drugs, and the majority had negative pregnancy outcomes.This can happen because the consumption of addictive drugs is not the only factor that affects infertility.
Another study stated that cocaine significantly increased the risk of primary tubal infertility among women with ovulatory dysfunction, tubal infertility, and age-matched fertile women, according to a population-based casecontrol study. 23Both marijuana and cocaine have been demonstrated to decrease fertility. 14,23,28According to a study, cocaine has an effect on decreasing pregnancy rates in women and adult spermatogenic forms in men. 28

Hormonal drugs in pregnancy outcome
After taking fertility medications, endogenous hormonal alterations may occur. 23,24Prior to the development of the synthetic production of reproductive hormones, there were many complications in reproduction, such as difficulty conceiving, instability of pregnancy, and complications at the time of birth; however, these complications have been reduced as a result of advancements in hormonal therapy. 29,30However, this findings revealed that there was no significant difference in pregnancy outcomes between wives who used hormonal drugs and those who did not.The majority had failed pregnancies.This is possible because the husband with UDT is the primary influencing factor.Infertility is linked to undescended testes because they impede gonocyte transformation. 1,2,31According to a study, hormonal drugs like letrozole are also commonly used to stimulate ovarian function and increase a woman's likelihood of becoming pregnant. 23,29Human infertility is predominantly treated with non-hormonal medications.This is due to the fact that hormonal therapy requires a series of injections, intensive monitoring, and severe side effects, such as ovarian hyperstimulation syndrome. 29festyle factors are not the only determinants of pregnancy outcomes.Particularly with severe infertility disorders such as UDT, the husband's influence can be crucial. 1,2Other factors in male infertility do not depend on age but excessive consumption of tobacco, alcohol, high fat consumption of food, obesity, strenuous exercise, sedentary lifestyle, contact with chemicals or poisons, stress or psychological disorders can trigger infertility problems. 32Therefore, interventions for infertility in husbands require psychological support in addition to medical methods such as ART. 33,34rgical correction before 1 year in Assisted Reproductive Technology Early detection and treatment of tests not dropped with orchiopexy between the ages of six and twelve months is thus critical to minimizing germ cell loss and increasing the individual's fertility index. 1 Two kind treatment of UDT have been used for many years and are accepted worldwide namely hormonal and surgical. 3,27,35This study no significant difference in pregnancy outcome on the factor of surgical correction before 1 year.Which can happen for various reasons.Most babies with UDT come to health care facilities after 1 year.Healthcare infrastructure in Indonesia for primary care (PHC) is mainly based on Puskesmas/Pratama clinics (Indonesian type of outpatient facilities) and primary care hospitals (class D), whereas advanced care (AHC) is mostly provided in level C/B (secondary/tertiary) hospitals and at the national level (class A hospitals. 36elays in bringing a baby with undescended testicles to a health care facility has an impact on fertility in adulthood.Treatment result should be evaluated at Available at: http://www.banglajol.info/index.php/BJMSleast one year after surgery and in childhood, primarily through examination. 3,27Scrotal position and absence of testicular atrophy are indicators of successful UDT surgical treatment. 3Complications from orchiopexy are uncommon approximately 1%. 3 Benefit of orchiopexy care is to pull the testicles down into the scrotum.It is implemented to prevent impaired spermatogenesis. 3,4,27,35ong-term studies are still needed to link fertility and paternity rates with early orchidopexy. 35

CONCLUSION
There was an association between infertility and UDT either unilaterally or bilaterally (p = 0.009).Most UDT husbands had a BMI in the overweight category and the average age was 28 and 29.Other factors, including smoking habit, alcohol consumption, addictive drug, hormonal drug and surgery correction before 1 year, had no significant effect on the success of pregnancy outcome (p > 0.05).Although the pregnancy outcome in unilateral and bilateral UDT patients was not statistically significant, clinically, the pregnancy outcome was better in husbands with unilateral UDT by IUI than IVF.This research's disadvantage was limited participants in both unilateral and bilateral retrospectively.Since Indonesia has not had sufficient data about UDT's male babies and some patients come to the hospital after 1 year old, the authors only observed their infertility patients in their centre.A larger data collection in many centers of Indonesia will be essential longitudinal analysis and approach to women with UDT husbands who undergo Assisted Reproductive Technology.

Table 1 .
Characteristics of UDT husband

Table 3 .
Data of pregnancy outcome in UDT Husband (Unilateral/Bilateral) correlated with the wive's life style