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 Table of Contents  
Year : 2021  |  Volume : 18  |  Issue : 4  |  Page : 186-190

Serum melatonin levels in women with infertility: A case–control study in a Nigerian university hospital

1 Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria
2 Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Submission31-Aug-2020
Date of Acceptance14-Jul-2021
Date of Web Publication09-Dec-2021

Correspondence Address:
Dr. Adegbenga Adetona Ajepe
Department of Obstetrics and Gynaecology, Lagos University Teaching Hospital, Idi-Araba, Lagos
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcls.jcls_67_20

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Background: Infertility is a public health issue in Nigeria, an environment of high daily sunlight exposure. This study objective was to assess the serum melatonin levels among infertile women and parous women in Nigeria. Methods: This was a case–control study involving 45 women of reproductive age with infertility and 45 parous women. Four milliliters of blood sample was collected from each of the participants between 1200 and 1600 h after written informed consent was obtained. Enzyme-linked immunosorbent assay technique using melatonin-specific monoclonal antibody was used for processing the samples. Obtained optical density was plotted and read off a standard curve. Data analysis was conducted with the Statistical Package for the Social Sciences version 23. A P < 0.05 was considered statistically significant. Results: The median serum melatonin values for women with infertility (27.86 pg/ml) and women without infertility (28.12 pg/ml) were similar (P = 0.735). Serum melatonin levels had insignificant negative correlation with age (P = 0.564), body mass index (P = 0.232), and daytime napping (P = 0.604). Melatonin levels had a nonstatistically significant positive correlation with duration of sleep (P = 0.789). Conclusion: This study found no significant difference in the serum melatonin levels in infertile and parous women. Melatonin supplementation in infertile women in our environment for the purpose of improving their fertility may not be recommended.

Keywords: Infertility, melatonin, Nigeria, supplementation

How to cite this article:
Ajepe AA, Okusanya BO, Abodunrin ON, Osanyin GE. Serum melatonin levels in women with infertility: A case–control study in a Nigerian university hospital. J Clin Sci 2021;18:186-90

How to cite this URL:
Ajepe AA, Okusanya BO, Abodunrin ON, Osanyin GE. Serum melatonin levels in women with infertility: A case–control study in a Nigerian university hospital. J Clin Sci [serial online] 2021 [cited 2023 May 28];18:186-90. Available from: https://www.jcsjournal.org/text.asp?2021/18/4/186/332072

  Introduction Top

Infertility is defined as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.[1] It is a major cause of emotional distress and marital disharmony, especially in Africa, where having children is highly valued. Although infertility is a major public health problem in Africa, concurrent high fertility rates in the subregion have led to neglect of infertility.[2] The WHO estimates that a quarter of couples in the developing countries are affected by infertility.[3] In Lagos, Nigeria, women with infertility accounted for 26.3% of all gynecology outpatient clinic consultations.[4] In Africa, infertility is often blamed on the woman even though the contributions from both partners are largely equal.[2] Huge resources, mostly out-of-pocket expenditures, are spent in the process of managing infertility by the affected couples. This impacts negatively on the economic situation of the affected couple making their lives more miserable. As a result, only the few wealthy couples usually have access to specialized care for infertility.[2]

Infertility is a complex medical condition with multifactorial etiology.[2] The causes of infertility can be categorized as male, tubal, ovulatory, and uterine factors and unexplained causes. It is noteworthy that some couples may have a combination of these factors causing their infertility.[5] Recent evidence suggests that oxidative stress may play some role in the etiopathogenesis of infertility.[6] Oxidative stress results from accumulation of reactive oxygen species or oxygen free radicals. Reactive oxidative species (ROS) are by-products of essential oxidative processes of the living cells.[7] The accumulation of oxygen free radicals may be due to overproduction of reactive oxygen species or depletion of naturally occurring antioxidants.[6] ROS have deleterious effects on the cells involved in the reproductive processes. It is also worthwhile to note that this oocytes aging is related to the age of the subjects.[8]

Melatonin is an important naturally occurring free radical scavenger. It is mostly produced from the pineal gland, at night (dark hours), with a major neuroendocrine function.[9] Some factors are known to affect the blood levels of melatonin. These factors include age, weight, diet, smoking, and alcohol consumption.[10] Yet, melatonin may play an important role in the regulation of hypothalamo–pituitary–ovarian axis.[8] Melatonin has been reported to play some roles in folliculogenesis, ovarian maturation, as well as embryo implantation and development.[11] Reduced levels of melatonin have been associated with increased levels of reactive oxygen species, which have deleterious effects on physiological processes and DNA structures of the cells including those involved in the processes of reproduction.[12] To support the roles of melatonin in infertility, low levels have been reported in cases of anovulation due to polycystic ovarian syndrome (PCOS),[13] while melatonin supplementation in the culture media for embryo of in vitro fertilization (IVF) led to improved success rates of the procedure.[14] In addition, melatonin exhibits immunomodulatory functions against infections[15] and acts against Chlamydia species to prevent subsequent tubal damage. This prevents tubal factor infertility.[10]

Studies evaluating the relationship of serum melatonin levels and female infertility are sparse. Melatonin has been linked with the production of progesterone in the follicle.[16] It is however equivocal in direct causation of infertility. While a study reported that serum melatonin levels were insignificantly higher in fertile women,[17] another study indicated much higher levels in women with PCOS than in women without infertility.[18] Despite this, when melatonin supplementation was used for women undergoing IVF cycles due to decreased ovarian reserves, it resulted in more and top-quality embryos than in women without melatonin supplementation.[19] This further compounds the association of melatonin to female fertility.

This study objective was to assess the serum melatonin levels among infertile women and parous women in Nigeria.

  Methods Top

In this case–control study, 45 women with a history of infertility were recruited from the gynecological outpatient clinic. Forty-five parous women, defined by spontaneous pregnancy and delivery in the preceding 12 months, were recruited from the family planning clinic and mothers who brought their children to the well-baby clinic of the same hospital. The sample size was arrived at using a formula of comparing means of serum melatonin levels between the two groups.[20]

Z(α/2) =1.96 at α =0.05; Z (1−β) =1.28; σ1 = 39.99 ng/L; σ2 = 52.41 ng/L; d = 35.00 ng/L.

Study participants were individually counseled about the study protocol, and informed consent was obtained.

Relevant data were collected with an interviewer-administered pro forma. Information collected included sociodemographic data, last menstrual period, past obstetric history, outcome of last pregnancy, weight, height, and sleeping pattern. Daytime napping was defined as any daytime sleep. Four milliliters of blood sample was collected from each of the participants between 1200 and 1600 h. After centrifugation, the sera were separated from all blood samples and stored at −20°C until analysis. Serum level of melatonin was determined using the Immuno-Biological Laboratories International kit made in Japan in 2017, according to the kit's instructions. Although melatonin exacts its effects through receptors on the follicles, serum and follicular levels of melatonin correlate well. This makes serum melatonin a good measure of the effect of the hormone on the follicles.[21] The assay utilizes a competitive enzyme-linked immunosorbent assay technique with a selected monoclonal antibody recognizing melatonin. The obtained optical density of the standard samples (y-axis, linear) was plotted against the women's samples concentration (x-axis, logarithmic) using an automated method. A standard curve was plotted, and the concentration of melatonin was read off directly from the curve.

Data obtained were analyzed using the Statistical Packages for the Social Sciences SPSS version 23. Chi-square (χ2) and Fisher's exact test, where applicable, were used to compare categorical variables between case and control groups, while the Student's t-test was used to compare the means of the continuous variables that were normally distributed. Nonparametric test (Mann–Whitney U) was used to compare the melatonin levels, which were not normally distributed, between the two categories. P < 0.05 was considered statistically significant.

Ethical approval for the study was given by the Health Research Ethics Committee of Lagos University Teaching Hospital (Ref. No.: ADM/DCST/HREC/APP/1354). This study was carried out in line with the Helsinki's Declaration.

  Results Top

Ninety (90) women participated in the study; 45 with infertility and 45 parous women. Majority of participants in each group had tertiary level of education, though participants who were parous had more professionals (44.4% vs. 28.9%; P = 0.044) than the infertile group. [Table 1] shows the sociodemographic characteristics of the participants. The mean age of women with infertility (34.95 ± 5.91) was similar (P = 0.109) to that of women without infertility (32.15 ± 4.54). The ages of the subjects ranged from 24 to 48 years. Further, the mean body mass index (BMI) of women with infertility (26.27 ± 4.49) and fertile women (25.34 ± 3.92) was similar (P = 0.301).
Table 1: Sociodemographic characteristics of participants in the study

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As in [Figure 1], the median melatonin value of women with infertility was 27.86 pg/ml (range 5–90 pg/ml) while that of fertile women was 28.12 pg/ml (range 2.5–97.5 pg/ml) (P = 0.735). [Table 2] shows the correlation between serum melatonin and independent factors. A negative insignificant correlation was found between melatonin level and age of the participants (r = −0.088; P = 0.564), as well as between melatonin level and BMI (r = −0.182; P = 0.232). Melatonin had an insignificant negative correlation with daytime napping (rs = −0.079; P = 0.604) though it had a positive correlation with night-sleep duration (rs = 0.042).
Figure 1: Distribution of melatonin level among fertile and subfertile women

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Table 2: The relationship between serum melatonin and factors evaluated

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  Discussion Top

This study showed a wide range of values of serum melatonin, despite the fact that the samples were drawn from the participants at a fixed time interval of the day. These values ranged between 2.5 pg/ml and 97.5 pg/ml which is in keeping with wide daytime reference range of the analyte and were not normally distributed.[22] Hence, a more precise measure of central tendency, the median, was used. The median level of serum melatonin in infertile women and their fertile controls (27.86 pg/ml, range 5–90 pg/ml, and 28.12 pg/ml, range 2.5–97.5 pg/ml, respectively) was not statistically significant. This finding was consistent with the finding of Soleimani Rad et al. in which no statistically significant difference was observed between melatonin levels of infertile and parous women.[17] They found a mean of 470.46 ± 39.99 pg/ml and 519.93 ± 52.11 pg/ml for infertile and parous women, respectively. This implies that melatonin levels at day time are similar in women, irrespective of their fertility.

The relationship between factors such as age, BMI, duration of night sleep, whether participants slept with the light switched on, and daytime napping and melatonin level was considered in this study. Although no statistically significant relationship was observed between melatonin level and all the factors assessed, negative correlation coefficients were observed for age and BMI. This implies that melatonin levels reduced as age and BMI increased among the participants, which is similar to the findings of Nogueira et al., who demonstrated a nonsignificant negative correlation between melatonin levels and BMI in females.[11] This negative correlation between age and melatonin levels may be due to progressive calcification of the pineal gland which occurs as people get older.[23] Conversely, positive correlation coefficients were observed for duration of night sleep, whether or not participants sleep with the light switched on, and participants had daytime napping. These indicate that melatonin levels may rise with increase in duration of night sleep, sleeping with light switched on, and having a nap in the day.

Melatonin levels obtained in this study were significantly higher than those obtained in a study conducted in Bulgaria.[24] This may be due to the calcification of the pineal gland which has been shown to proceed at a faster rate with aging, in the Caucasians compared to Black people.[25] Melatonin supplementation may not be necessary in the management of subfertile women because they have similar levels of melatonin as in fertile women. This submission is supported by the conclusion of a meta-analysis of randomized controlled trials conducted by Showell et al., in which oral supplements of some antioxidants, including melatonin, were not shown to improve fertility outcomes for infertile women.[26]

  Conclusion Top

Melatonin levels in infertile women in this study had a very wide range, and the median value was like that of fertile women. There were also no significant relationships between melatonin levels and age, daytime napping, switching on light during night sleep, and BMI.

A limitation of this study was the timing of the sample collection for analysis for melatonin. Samples drawn between midnight and 9:00 am would have provided the optimum values of melatonin assay.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Hammarberg K, Kirkman M. Infertility in resource-constrained settings: Moving towards amelioration. Reprod Biomed Online 2013;26:189-95.  Back to cited text no. 2
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Lo Cicero A, Delevoye C, Gilles-Marsens F, Loew D, Dingli F, Guéré C, et al. Exosomes released by keratinocytes modulate melanocyte pigmentation. Nat Commun 2015;6:7506.  Back to cited text no. 10
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Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, et al. The role of melatonin as an antioxidant in the follicle. J Ovarian Res 2012;5:5.  Back to cited text no. 12
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Kim MK, Park EA, Kim HJ, Choi WY, Cho JH, Lee WS, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reprod Biomed Online 2013;26:22-9.  Back to cited text no. 14
Fernando S, Rombauts L. Melatonin: Shedding light on infertility? – A review of the recent literature. J Ovarian Res 2014;7:98.  Back to cited text no. 15
Fang L, Li Y, Wang S, Yu Y, Li Y, Guo Y, et al. Melatonin induces progesterone production in human granulosa-lutein cells through upregulation of StAR expression. Aging (Albany NY) 2019;11:9013-24.  Back to cited text no. 16
Soleimani Rad S, Abbasalizadeh S, Ghorbani Haghjo A, Sadagheyani M, Montaseri A, Soleimani Rad J. Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women. Iran J Reprod Med 2015;13:439-44.  Back to cited text no. 17
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Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: Relation to human obesity. Obes Rev 2011;12:167-88.  Back to cited text no. 24
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  [Figure 1]

  [Table 1], [Table 2]


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