Common Autoimmune Antibodies in Unexplained Infertile Female Patients in Saudi Arabia - Cureus

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Background: Unexplained pistillate infertility is simply a devastating wellness occupation that has go progressively prevalent worldwide with nary circumstantial mentation contempt broad evaluations. Recent information suggest that serum autoimmune antibodies are often recovered successful patients with unexplained pistillate infertility.

Objectives: This survey aims to place the prevalence of communal autoantibody abnormalities successful females with unexplained infertility successful Saudi Arabia.

Methods: A cross-sectional survey was conducted connected pistillate patients with unexplained infertility sequentially referred to the allergy and immunology session astatine King Abdulaziz University Hospital (KAUH). Demographics, objective characteristics, and 12 communal autoantibody immunological tests were described arsenic frequence and percentage. The chi-square trial was applied to measure immoderate associations.

Results: A full of 119 females with unexplained infertility were studied; of those, 97 (81.5%) had secondary infertility. Their mean property was 33.9 ± 5.6 years ranging from 23 to 49 years. The wide prevalence of a precocious level of astatine slightest 1 autoantibody (above the mean range) was 84%. The predominant precocious autoantibodies were antithyroglobulin successful 42 (35.3%), antithyroid microsomal successful 41 (34.5%), beta 2 glycoprotein IgM successful 40 (33.6%), antigliadin IgA successful 32 (26.9%), antinuclear successful 22 (18.5%), and anticardiolipin IgM successful 18 (15.1%) of the participants. The pursuing important associations were recovered successful our study: secondary infertility with beta 2 glycoprotein (p = 0.022), property with antithyroglobulin (p = 0.027), and the fig of pregnancies with anti-tissue transglutaminase IgG and antigliadin IgA (p = 0.015 and p = 0.043, respectively).

Conclusion: A precocious level of astatine slightest 1 autoantibody was detected successful the bulk of females with unexplained infertility. Antithyroid, antiphospholipid, antigliadin, and antinuclear autoantibodies were the astir common autoantibodies. These findings whitethorn promote autoantibody screening successful infertile females to observe immoderate imaginable immunopathology successful further objective studies.

Introduction

Infertility is defined arsenic the nonaccomplishment to conceive aft 12 months oregon much of regular unprotected intersexual intercourse, and it has a planetary mean prevalence of astir 15% [1]. In Saudi Arabia, the infertility rates among women are connected the rise and are presently up to 18.9-23.3% [2,3].

The astir devastating benignant of infertility, which is besides connected the emergence worldwide, is unexplained infertility, which accounts for astir 10-17% of infertile females [4,5]. The dilemma is the lack of a wide crushed for infertility contempt thorough evaluations and treatments [5,6]. The attack to attraction is perpetually changing arsenic caller grounds describes antithetic imaginable etiologies with objective associations, indicating newer laboratory investigations [5,6].

It has been good established that aesculapian disorders associated with autoimmune antibodies, specified arsenic systemic lupus erythematosus and antiphospholipid syndrome, relationship for immoderate of the infertility cases [5]. Over the past 20 years, nonspecific autoimmunity, defined arsenic the beingness of autoantibodies successful a serum illustration without the objective criteria of a defined disease, has been described successful immoderate infertile women [7].

A caller systematic reappraisal has shown that serum autoantibodies, including antithyroid, antiphospholipid, and antinuclear antibodies, were much often recovered successful females with unexplained infertility [7]. The beingness of antinuclear antibodies is regarded arsenic a emblematic diagnostic of autoimmunity successful recurrent gestation nonaccomplishment [8]. Moreover, antisperm antibodies arsenic good arsenic celiac illness antibodies person been linked to unexplained infertility cases [9,10]. Many studies person been conducted to clarify the relation betwixt these autoantibodies with not lone recurrent abortions but besides with repeated IVF failures, but the findings person been debatable [7,11].

According to galore planetary guidelines, it is not routinely recommended to behaviour immunological investigations successful the attack to pistillate infertility [12,13]. Nevertheless, the American and European societies for reproduction urge screening for antiphospholipid antibodies lone aft 2 gestation losses, portion galore European societies of obstetricians and gynecologists urge this probe aft 3 gestation losses [14]. More recently, immoderate of these guidelines urge screening for antithyroid antibodies and antinuclear antibodies successful recurrent gestation losses for exploratory purposes [15]. Moreover, immoderate authors person precocious recommended ordering immoderate autoimmune trial workups aft 2 successful vitro fertilization (IVF) failures [11].

However, immunological investigations successful females with unexplained infertility are seldom considered successful infertility clinics, contempt the anticipation of soundless immunological irregularities that mightiness beryllium easy underestimated by galore physicians. Hence, this task was intended to research the prevalence of immoderate imaginable communal auto-immunological laboratory abnormalities successful females with unexplained infertility successful Saudi Arabia.

Materials & Methods

Study plan and setting

This is simply a cross-sectional survey of pistillate patients diagnosed with unexplained infertility astatine King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. It was conducted from May to August 2022. KAUH is an 800-bed hospital, 1 of the tertiary referral and teaching centers successful the occidental portion of Saudi Arabia.

The inclusion criteria for the participants specified each females aged 18 to 45 years aged with unexplained superior and secondary infertility sequentially referred to the allergy and immunology session astatine KAUH by infertility physicians to regularisation retired immunological abnormalities. According to the WHO, superior infertility refers to females who person ne'er fallen pregnant, portion secondary infertility refers to females who person been large erstwhile [1].

The exclusion criteria specified infertility cases with identified well-known causes different than abnormal immunological tests and with incomplete immunological laboratory results and missing follow-up.

The illustration size and sampling procedures

A full of 136 pistillate patients with unexplained infertility referred from galore infertility specialists were recruited astatine KAUH. Of these, 17 were excluded according to our inclusion and exclusion criteria.

Data collection

The patient’s demographic, clinical, and laboratory information were collected done physics aesculapian grounds files. Data organisation and postulation were conducted with the usage of physics Google Sheets (Google, Mountain View, CA) divided into 3 sections. The archetypal conception collected the patient’s demographic data. The 2nd conception consisted of 8 points of objective information, namely, infertility type, fig of pregnancies, surviving children, preterm labor, abortions, stillbirths, intracytoplasmic sperm injection (ICSI), and intrauterine insemination (IUI). The 3rd conception was related to 12 communal autoantibody immunological tests, and the autoantibodies were beta 2 glycoprotein antibody IgG, beta 2 glycoprotein antibody IgM, anticardiolipin antibody IgG, anticardiolipin antibody IgM, antithyroglobulin antibody, antithyroid microsomal antibody, antinuclear antibodies, antisperm antibody, anti-tissue transglutaminase antibody IgA, anti-tissue transglutaminase antibody IgG, antigliadin antibody IgA, and antigliadin antibody IgG. Testing for autoantibodies successful the serum of the studied patients was performed astatine the immunology laboratory astatine KAUH.

Data analysis

The statistical investigation consisted of 2 parts. First, a descriptive investigation of each the subjects included successful the survey was conducted. Frequency and percent were calculated for categorical factors, portion means and modular deviation were calculated for continuous variables. Thereafter, the relation betwixt autoantibody laboratory tests and the sociodemographic characteristics and the obstetrics gynecological inheritance variables were estimated utilizing the chi-square test. All p-values < 0.05 were considered statistically significant. The Statistical Package for Social Sciences (SPSS) mentation fig 26 (IBM Corp., Armonk, NY) was utilized for each information analyses.

Research ethics

The Research Committee of the Unit of Biomedical Ethics of KAUH approved the survey connection (reference number: 331-22). Participation was voluntary, participants were informed astir the objectives and methodology of the study, and they were not offered immoderate incentives to participate. Verbal consent was obtained from each subordinate earlier the information collection.

Results

A full of 136 pistillate patients with unexplained infertility referred from galore infertility specialists were recruited astatine KAUH. Of these, 17 were excluded: 10 owed to a deficiency of follow-up and 7 for insufficient immunological laboratory results. In total, 119 pistillate patients consented to and participated successful this research. The participants' ages ranged from 18 to 45 years, with a mean ± SD of 33.9 ± 5.6 years.

The information were divided into nationalities; 103 patients (86.6%) were Saudi citizens, and 16 (13.4%) were non-Saudi residents. Regarding the spot of residence of the patients, 69 (58.0%) were from Jeddah, 10 (8.4%) were from Makkah, 10 (8.4%) were from Taif, and 30 (25.2%) were from different cities successful Saudi Arabia.

Regarding infertility types, 22 patients (18.5%) had been diagnosed with superior infertility and 97 (81.5%) with secondary infertility. Of the studied patients, 72 (60.5%) had nary surviving children, and 47 (39.5%) had astatine slightest 1 surviving child. Recurrent abortions (more than two) were the predominant diagnostic successful 43 patients (36.1%), portion 34 patients (28.6%) had nary abortions. There were 67 patients (56.3%) who had received astatine slightest 1 ICSI, and 23 (19.3%) had received 1 oregon much IUI (Table 1).

Sociodemographic and infertility background Number Percentage
Age successful years    
<35 61 51.3%
≥35 58 48.7%
Marital presumption (duration successful years)    
Less than 5 years 36 30.3%
5-10 years 35 29.4%
>10 years 48 40.3%
Nationality    
Saudi 103 86.6%
Non-Saudi 16 13.4%
City    
Jeddah 69 58.0%
Makkah 10 8.4%
Taif 10 8.4%
Others 30 25.2%
Infertility type    
Primary 22 18.5%
Secondary 97 81.5%
Number of pregnancies    
None 22 18.5%
1-2 pregnancies 25 29.4%
3-4 pregnancies 22 26.9%
>4 pregnancies 30 25.2%
Number of surviving children    
No babies 72 60.5%
1-3 babies 42 35.3%
>3 babies 5 4.2%
Number of abortions    
No abortions 34 28.6%
1-2 abortions 42 35.3%
>2 abortions 43 36.1%
Number of stillbirths    
None 109 91.6%
Present 10 8.4%
Number of preterm    
None 111 93.3%
Present 8 6.7%
Number of ICSI    
None 52 43.7%
1-2 34 28.6%
>2 33 27.7%
Number of IUI    
None 96 80.7%
1-2 17 14.3%
>2 6 5.0%

From a full of 12 autoantibody laboratory tests, 100 patients had precocious levels of astatine slightest 1 autoimmune antibody (above the mean range), which is equivalent to 84% of the studied patients. The antithyroglobulin antibody, which was recovered successful 42 patients (35.3%), was the commonest, followed by the antithyroid microsomal antibody successful 41 patients (34.5%), portion the beta 2 glycoprotein antibody IgM, recovered successful 40 patients (33.6%), was the 3rd communal (Table 2).

Autoantibodies Normal level High level
Number Percent Number Percent
Antithyroglobulin antibody 77 64.7% 42 35.3%
Antithyroid microsomal antibody 78 65.5% 41 34.5%
Beta 2 glycoprotein antibody IgM 79 66.4% 40 33.6%
Antigliadin antibody IgA 87 73.1% 32 26.9%
Antinuclear antibodies 97 81.5% 22 18.5%
Anticardiolipin antibody IgM 101 84.9% 18 15.1%
Anticardiolipin antibody IgG 108 90.8% 11 9.2%
Antigliadin antibody IgG 109 91.6% 10 8.4%
Anti-tissue transglutaminase antibody IgA 111 93.3% 8 6.7%
Anti-tissue transglutaminase antibody IgG 117 98.3% 2 1.7%
Beta 2 glycoprotein antibody IgG 117 98.3% 2 1.7%
Antisperm antibody 118 99.2% 1 0.8%

There was a statistically important relation betwixt the beta 2 glycoprotein antibody IgM and secondary infertility (p = 0.022). Moreover, the antithyroglobulin antibody was recovered to beryllium accrued successful women implicit the property of 35 years, compared to younger women (p = 0.027). In addition, the fig of pregnancies was statistically importantly associated with the anti-tissue transglutaminase antibody IgG and antigliadin antibody IgA (p = 0.015 and p = 0.043, respectively). Finally, the anti-tissue transglutaminase antibody IgA was statistically importantly associated with the fig of ICSI cycles (p = 0.024) (Tables 3, 4).

Autoantibodies Age successful years Marital presumption (duration successful years) Infertility type
<35 ≥35 P-value <5 5-10 >10 P-value Primary Secondary P-value
Beta 2 glycoprotein antibody IgG                    
Normal 60 57 0.739 36 33 48 0.087 22 95 0.663
High 1 1 0 2 0 0 2
Beta 2 glycoprotein antibody IgM                    
Normal 37 24 0.122 22 27 30 0.274 10 69 0.022*
High 24 16 14 8 18 12 28
Anticardiolipin antibody IgG                    
Normal 55 53 0.536 32 30 46 0.261 19 89 0.330
High 6 5 4 5 2 3 8
Anticardiolipin antibody IgM                    
Normal 52 49 0.555 29 32 40 0.410 19 82 0.564
High 9 9 7 3 8 3 15
Antithyroglobulin antibody                    
Normal 45 32 0.027* 25 26 26 0.129 14 63 0.546
High 16 26 11 9 22 8 34
Antithyroid microsomal antibody                    
Normal 44 34 0.087 29 21 28 0.075 14 64 0.509
High 17 24 7 14 20 8 33
Antinuclear antibodies                    
Normal 50 47 0.541 27 27 43 0.171 19 78 0.380
High 11 11 9 8 5 3 19
Antisperm antibody                    
Normal 60 58 0.513 35 35 48 0.313 22 96 0.815
High 1 0 1 0 0 0 1
Anti-tissue transglutaminase antibody IgA                    
Normal 57 54 0.613 34 33 44 0.846 19 92 0.164
High 4 4 2 2 4 3 5
Anti-tissue transglutaminase antibody IgG                    
Normal 61 56 0.235 36 34 47 0.620 22 95 0.663
High 0 2 0 1 1 0 2
Antigliadin antibody IgA                    
Normal 47 40 0.216 27 26 34 0.897 14 73 0.197
High 14 18 9 9 14 8 24
Antigliadin antibody IgG                    
Normal 56 53 0.596 34 31 44 0.672 19 90 0.273
High 5 5 2 4 4 3 7
Autoantibodies Pregnancies Abortions Stillbirth ICSI IUI
  0 1 2 3 4 5-14 P 0 1-2 >2 P 0 ≥1 P 0 1-2 >2 P 0 1-2 >2 P
Beta 2 glycoprotein antibody IgG                                            
Normal 22 18 17 14 17 29 0.547 34 42 41 0.166 107 10 0.838 50 34 33 0.270 94 17 6 0.784
High 0 0 0 1 0 1 0 0 2 2 0 2 0 0 2 0 0
Beta 2 glycoprotein antibody IgM                                            
Normal 10 11 12 13 10 23 0.098 18 29 32 0.127 72 7 0.551 38 21 20 0.394 60 15 4 0.117
High 12 7 5 2 7 7 16 13 11 37 3 14 13 13 36 2 2
Anticardiolipin antibody IgG                                            
Normal 19 16 16 12 16 29 0.499 31 39 38 0.771 98 10 0.364 47 32 29 0.673 85 17 6 0.234
High 3 2 1 3 1 1 3 3 5 11 0 5 2 4 11 0 0
Anticardiolipin antibody IgM                                            
Normal 19 16 14 13 13 26 0.925 29 34 38 0.632 94 7 0.176 44 31 26 0.367 80 15 6 0.497
High 3 2 3 2 4 4 5 8 5 15 3 8 3 7 16 2 0
Anti-thyroglobulin antibody                                            
Normal 14 11 12 13 12 15 0.249 22 30 25 0.440 70 7 0.504 32 23 22 0.814 64 10 3 0.610
High 8 7 5 2 5 15 12 12 18 39 3 20 11 11 32 7 3
Antithyroid microsomal antibody                                            
Normal 14 11 12 12 11 18 0.823 21 29 28 0.800 73 5 0.228 38 21 19 0.294 64 10 4 0.820
High 8 7 5 3 6 12 13 13 15 36 5 14 13 14 32 7 2
Antinuclear antibodies                                            
Normal 19 15 12 13 14 24 0.843 30 35 32 0.280 89 8 0.586 42 28 27 0.982 79 14 4 0.630
High 3 3 5 2 3 6 4 7 11 20 2 10 6 6 17 3 2
Antisperm antibody                                            
Normal 22 18 17 15 16 30 0.301 34 42 42 0.410 108 10 0.916 51 34 33 0.522 95 17 6 0.886
High 0 0 0 0 1 0 0 0 1 1 0 1 0 0 1 0 0
Anti-tissue transglutaminase antibody IgA                                            
Normal 19 17 16 13 17 29 0.473 31 38 42 0.352 102 9 0.516 52 29 30 0.024* 89 17 5 0.329
High 3 1 1 2 0 1 3 4 1 7 1 0 5 3 7 0 1
Anti-tissue transglutaminase antibody IgG                                            
Normal 22 18 17 13 17 30 0.015* 34 41 42 0.666 107 10 0.838 51 33 33 0.635 94 17 6 0.784
High 0 0 0 2 0 0 0 1 1 2 0 1 1 0 2 0 0
Antigliadin antibody IgA                                            
Normal 14 12 14 9 10 28 0.043* 21 31 35 0.154 82 5 0.093 43 21 23 0.088 70 13 4 0.893
High 8 6 3 6 7 2 13 11 8 27 5 9 13 10 26 4 2
Antigliadin antibody IgG                                            
Normal 19 16 17 13 16 28 0.662 30 38 41 0.508 101 8 0.199 49 31 29 0.586 87 17 5 0.331
High 3 2 0 2 1 2 4 4 2 8 2 3 3 4 9 0 1

Discussion

Unexplained infertility, chiefly with recurrent gestation losses and implantation failures, constitutes a peculiarly challenging and devastating taxable successful reproductive medicine and places a important affectional load connected the couples involved.

Recent probe has shown that a palmy gestation includes an immunologically unsocial signifier of impermanent tolerance mechanics toward the implanting fetus, to let implantation and the consequent improvement of the gestation without rejection [16]. Various caller studies person suggested that an overactive immune strategy successful immoderate females whitethorn summation the trouble successful conceiving oregon summation the hazard of termination [7]. This suggests that determination could beryllium a amended accidental of occurrence by investigating the immune strategy and trying immunomodulating therapies.

In this cross-sectional study, 12 antithetic auto-immunological antibodies laboratory tests were done connected 119 pistillate patients with unexplained infertility. The wide prevalence of astatine slightest 1 affirmative trial effect for autoimmune antibodies was 84%, which corresponds to the bulk of the studied group. Two erstwhile akin studies done successful France explored less autoantibodies and recovered that the prevalence of immoderate autoantibodies was 32-33% [17,18]. This mightiness bespeak the complexity of the cases referred to an immunology adept and the request for a broader enactment of and much circumstantial radical of autoantibodies.

In this study, the astir predominant precocious level of autoantibodies was antithyroid (antithyroglobulin and antithyroid microsomal) antibodies, which were recovered successful one-third of the studied group. Interestingly, the levels of antithyroglobulin antibodies accrued with an summation successful the women’s ages. In 2 erstwhile studies connected unexplained infertility, 29% of the cases were recovered to person antithyroid peroxidase antibodies [18,19]. The effects of thyroid antibodies connected infertility, IVF outcome, and ongoing gestation are controversial, but, if these antibodies coexist with hyperthyroidism oregon subclinical hypothyroidism, they could impair fertility [11,20].

In this study, antiphospholipid antibodies were the 2nd astir predominant autoantibodies recovered successful precocious levels successful astir one-third of the studied group, peculiarly B2 glycoprotein, and much than anti-cardiolipin antibodies, which were reported successful erstwhile akin studies to beryllium higher than 22-23% [19,21]. Interestingly, the studied radical showed a important narration betwixt B2 glycoprotein and secondary infertility. Although immoderate studies person shown that antiphospholipid antibodies bash not correlate with gestation and IVF outcomes, different studies person shown a little objective gestation complaint [11,20].

The prevalence of precocious levels of antinuclear antibodies recovered successful this survey was 18.5%, which is adjacent to what was recovered successful a caller ample meta-analysis that recovered a 22% prevalence wrong the recurrent gestation nonaccomplishment radical [8]. Moreover, a systemic reappraisal has shown that the beingness of anti-nuclear antibodies was associated with less objective pregnancies and higher miscarriage rates aft IVF [8,20]. More specifically, celiac antibodies specified arsenic the anti-tissue transglutaminase IgA were recovered successful lone 6.4% of the studied patients, which correlates with erstwhile studies that recovered 2-8% [10]. High levels of antigliadin IgA, a little circumstantial celiac antibody, were recovered successful astir a 4th of the studied patients. In contrast, a caller meta-analysis conducted successful 2021 has shown that celiac illness is not much communal successful infertile women than successful the wide population, which is successful opposition to what was recovered successful 2 erstwhile meta-analyses [22]. However, successful this study, precocious levels of anti-tissue transglutaminase IgG and anti-gliadin IgA antibodies were associated with an accrued fig of some earthy and assisted pregnancies, and anti-tissue transglutaminase antibody IgA was associated with an accrued fig of ICSI rhythm failures.

However, immoderate autoantibodies were not communal successful this studied radical specified arsenic beta 2 glycoprotein antibody IgG, anti-tissue transglutaminase IgG, and antisperm antibodies. Hence, the show of these autoantibody tests whitethorn not beryllium regular successful patients with unexplained infertility, unless it is for further probe purposes.

Determining communal immunological irregularities whitethorn assistance successful establishing a line arsenic to erstwhile these autoimmunological markers should beryllium utilized and which types to see to widen the position of the doc to beryllium capable to found the narration betwixt the immune strategy and unexplained infertility successful females.

It should beryllium noted that this probe was taxable to respective limitations that included utilizing convenient sampling from an allergy immunology clinic, missing files, a tiny illustration size, and a non-randomized study.

Conclusions

In conclusion, this cross-sectional survey has revealed that raised level of astatine slightest 1 autoantibody was a communal uncovering successful this convenient illustration of females with unexplained infertility. Among those, antithyroid, antiphospholipid, antigliadin, and antinuclear autoantibodies were the commonest autoantibodies. Encouraging the recognition and isolation of circumstantial autoimmunological pathways of maternal immune responses to the fetus whitethorn payment the objective probe attack and the absorption of females with unexplained infertility. Further large-scale and well-designed randomized controlled objective studies that analyse the benefits of autoimmunological evaluations successful females with infertility are indispensable earlier much elaborate recommendations tin beryllium created.

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