Introduction

Infertility is major problem in India. Infertility refers to the condition where a couple is not able to conceive after 12 months of unprotected sexual intercourse.^[1] Approximately 5-15% of all married couples in country are facing this problem.^[2] Generally, the social stigma is attached to female partner but around 30% males are also contributing to infertility.^[2] Declining fertility rate is a serious concern in both males and females and needs urgent redressal.

Male factor infertility has been on rise recently and trend towards declining semen quality is revelation of deteriorating reproductive health.^[3] It has promoted reproductive research to scrutinize the underlying causes to bring about effective therapeutic and preventive measures.

Several factors contribute to global declining trends in semen parameters however few pathological, environmental, and life style associated factors have been identified ^[4] which affect the hormonal milieu in the male reproductive organ thereby affecting spermatogenesis. Endogenous hormones play important role in regulation of male reproductive function by influencing steroid genesis or/and spermatogenesis process and in that purview role of thyroid hormones has been specifically investigated.^[5]

According to studies Thyroid hormone leads to alteration in semen parameters by genomic and non-genomic pathways. Genomic effects are produced by binding of T3 to TR receptor in nucleus of Sertoli and Leydig cells. Non genomic effects result from binding of thyroid hormones to nonnuclear receptors present in the cytoplasmic membrane, cytoplasm, mitochondria and cytoskeleton of the sperm. This way it enhances the synthesis of cyclic adenosine monophosphate (cAMP) and increases release of calcium and ultimately affect sperm motility.^[6] Thyroid hormones also contribute to regulation of the redox status of testis that relies on a number of antioxidant systems and is required for optimum spermatogenesis.^[7]

The two most common types of thyroid dysfunction include hyperthyroidism and hypothyroidism; the former may result in oligozoospermia, asthenozoospermia, and/or teratozoospermia and reduced semen volume while later may lead to teratozoospermia and decreased sperm motility.^[7] The affected parameters reverted to normal after the treatment.^[8]

Several studies have been reported to evaluate the role of thyroid hormones on physiological male reproductive function but very few have targeted the direct effect of thyroid dysfunction on semen parameters and quality. Thus, in order to further evaluate the role of Thyroid hormones in optimizing spermatogenesis and to investigate the effect of Thyroid dysfunction on semen quality the study was undertaken.

Materials and Methods

We conducted a Prospective cohort study between November 2020 to November 2022. All the males of infertile couple attending infertility clinic outpatient department (OPD) of Jawaharlal Nehru Medical College and Hospital, Aligarh, Uttar Pradesh, India were taken as subjects. Ethical clearance from the Institutional Ethics Committee (IEC) of Jawaharlal Nehru Medical College and hospital was taken in order to conduct this study. Patients were enrolled after taking written informed consent and satisfying inclusion and exclusion criteria.

Results

In the present study the, multiple characteristics of the study population (N=100) were evaluated and tabulated in [Table 1].

In present study, mean age distribution of the study subjects (N=100) was 34.27+5.3 yrs. Mean BMI was 25.99+2.97. Majority of the population was literate (83%). Primary infertility was the major concern of the study population. The Mean value of serum TSH (mU/L) in study subjects was 3.39 ± 2.57 with median (25th-75th percentile) of 2.6(2.05-3.92).

Of 100 subjects, 22(22.00%) were smokers where 15 were moderate, 6 light and 1heavy smoker and 8(8.00%) were alcoholics where 7 were mild and 1 moderate drinker respectively. The number of Euthyroid cases were 73(73.00%), whereas 24(24.00%) and 3(3.00%) were hypothyroid and hyperthyroid respectively, diagnosed on the basis of serum TSH and T4 levels. No cases of subclinical hypothyroidism were reported.

Detailed semen analysis showed normal range of Total Sperm concentration (10⁶/mL) in 67.00% of cases while 33(33.00%) subjects had any one value below the reference range and thus were categorized as abnormal or Low. Mean value of Total sperm concentration (10⁶/mL) was 34.67 ± 26.54 while median (25th-75th percentile) was 35(12.8-46.5).

Percentage total motility in 55(55.00%) cases was normal, whereas 45(45.00%) of them had motility below the 5th percentile of reference ranges. Mean value of progressive motility (%) of study subjects was 35.51 ± 24.65 with median (25th-75th percentile) of 30(15-58.5).

The study population was further categorized in to Euthyroid (N=73), Hypothyroid (N=24) and Hyperthyroid (N=3) groups and various parameters were compared and analyzed in the three groups as given in [Table 2].

Mean age and BMI were comparable in all the groups using One-way ANNOVA test with p-value < 0.05. Qualitative variables namely smoking index and alcohol consumption were compared using Chi square test and no significant difference was noted (P-value 0.882 and chi-0.092).

Semen parameters were as follows, Mean value of Total sperm concentration (TSC) in Euthyroid, Hypothyroid and Hyperthyroid grp was 39.6125±26.54, 14.4029±18.14 and 17.6000±10.83 while Total percentage progressive motility was 40.751±24.64, 14.4029±19.96 and 28±36.49. Semen volume was 2.71+1.46, 2.87+2.1 and 2.5+1.5 respectively.

Correlation of TSH with semen parameters (TSC, sperm motility, semen volume and morphology (N=100)

The correlation between TSH and Total sperm cell concentration as well as motility in total study population (N=100) was established on application of Pearsons correlation and a significant strong negative correlation was found (r= -.276, p=0.005), while with motility, a significant moderately strong negative correlation (r=-.310, p=0.002) was found as demonstrated in [Table 3]. It can be postulated that higher values of TSH (Hypothyroidism) have inverse effect on Total sperm count and motility of sperms or vice versa. On the scatter plot diagram, the inverse correlation between thyroid levels and total sperm count and sperm motility can be seen. ([Figure 1], [Figure 2]).

Mean serum TSH was 3.392±.57 and mean Semen volume was 2.71± 1.46 in (N=100) and on application of Pearson correlation test no correlation could be elucidated while similar results were obtained with morphology.

	sTSH	T.Sperm conc	Motility
sTSH	Pearson Correlation	1	-.276**	-.310**
Sig. (2-tailed)		.005	.002
N	100	100	100
Total sperm conc	Pearson Correlation	-.276**	1	.482**
P-value-Sig. (2-tailed)	.005		.000
N	100	100	100
Motility	Pearson Correlation	-.310**	.482**	1
P value-Sig. (2-tailed)	.002	.000
N	100	100	100

Table 3 Correlation of TSH with TSC and motility

Discussion

In the study the prevalence of Male factor infertility as suggested by abnormal semen parameters was 33% however global data survey mentions it to be between 7-15%.^[11] In 2019, the global prevalence of male infertility was estimated to be 56,530.4 thousand (95% UI: 31,861.5–90,211.7).^[12] The higher values in our study may be attributed to the targeted population of infertile couple where expected fertility is diminished as compared to the general population.

The mean age of the study population was 34.27+5.3 yrs and it was in coherence with multiple studies where comparable age groups were documented^[13], ^[14], ^[15] as this age group strives to obtain pregnancy and in the event of inability to conceive, reports promptly. In this study Age did not affect the semen quality, as suggested by Pearson correlation (Semen volume r-value 0.153 and p-value 0.129, TSC- r-value 0.058 and p-value 0.566, Motility r-value -0.04 and p-value 0.693) however other studies have reported statistically significant age-related declines in the aforementioned parameters, whereas others have reported no changes or rarely, even improvements in some parameters, with age.^[16], ^[17], ^[18], ^[19], ^[20], ^[21]

This disparity may be due to heterogeneity of the data, racial and geographical differences.

Further mean BMI of the group was 25.99+2.97, belonged to overweight category and correlation with semen quality using Pearson Correlation showed negative but insignificant correlation with TSC and motility (TSC-r--0.104 and p- 0.305 motility r-value-0.111 and p-value 0.273). Several studies supported the theory of BMI (Obese grp) affecting semen quality^[22], ^[23], ^[24] unlike ours. The difference was presumably due lack of subjects in obese grp.

Prevalence of Thyroid abnormalities namely Hypothyroidism and Hyperthyroidism in the study population was 24 and 3 respectively. Prevalence of aforementioned abnormalities among men in general population is around 1.9-6.2%.^[25] This difference from the general data is due to specified infertile population being targeted where Thyroid dysfunction is presumably more. Moreover, Thyroid hormones are known to be responsible for optimum reproductive function and therefore the study was conducted to evaluate the effect of thyroid abnormalities on the semen quality.

As mentioned earlier study population was divided in to 3 groups based on Thyroid abnormalities (Euthyroid, Hypothyroid and Hyperthyroid)

Conclusion

Evaluation of the male partner is an essential element in assessment of infertile couple. The presence of subtle abnormalities in males may not manifest as abnormal semen analysis but may result in inability of the couple to conceive. Conversely semen abnormalities may not always result in infertility. Therefore, assessing the male partner is a tricky affair.

Hormonal assessment is not a part of recommendation unless specifically indicated. Evidences suggest that abnormal hormonal milieu may affect the semen quality, specifically thyroid abnormalities which may or may not manifest as grossly abnormal semen analysis and therefore refraining from assessing Thyroid status may delay the appropriate workup of the male partner.

Role of thyroid hormones in optimization of testicular function has been well elucidated in previous studies and is also highlighted in the present study.

To conclude male factors should be thoroughly evaluated with due significance to thyroid function assessment after proper counselling. The screening of thyroid function might be reconsidered in light of available evidences from the present study and should be further confirmed by large scale studies.

Source of Funding

None.

Conflict of Interest

None.

Acknowledgement

All the work and contributions are acknowledged.