Innovative utilization of menstrual blood for determination of HbA1c, FSH, LH, AMH cholesterol,CRP quantitiesin infertile women with no access to medical facilities/cost factor/fear of pricks for facilitating early access for assisted reproductive technol

Innovative utilization of menstrual blood for determination of HbA1c, FSH, LH, AMH cholesterol,CRP quantitiesin infertile women with no access to medical facilities/cost factor/fear of pricks for facilitating early access for assisted reproductive technology(ART)-advantages of simultaneous testing of ones needing blood/serum- A Short Communication

Dr. Kulvinder Kochar Kaur*1, Dr. Gautam Nand Allahbadia2, Dr. Mandeep Singh3

 

2. Dr. Gautam Nand Allahbadia M.D.(Obstt&Gynae),D.N.B, Scientific Director, Ex-Rotunda-A Centre for Human Reproduction. 672,Kalpak Garden,Perry Cross Road, Near Otter’s Club,Bandra(W)-400040, MUMBAI, INDIA.

3. Dr. Mandeep Singh M.D.DM.(Std)(Neurology), Consultant Neurologist,  Swami Satyanand Hospital, Jalandhar-144001, Punjab, India.

 

*Correspondence to: Dr. Kulvinder Kochar Kaur, M.D (Obstt&Gynae, specialist reproductive endocrinology & Infertility specialist). Scientific Director, Dr Kulvinder  Kaur Centre For Human Reproduction. 721, G.T.B. Nagar, Jalandhar-144001, Punjab, India.


Copyright
© 2024: Dr. Kulvinder Kochar Kaur. This is an open access article distributed under the Creative Commons Attribution  License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original   work is properly cited.

Received:  19 May 2024

Published: 01 June 2024  

Abstract

Recently, Nasseri et al. have been pursuing the determination of HbA1c FSH, LH, AMH cholesterol,CRP quantities  in infertile -advantages of simultaneous testing of ones needing blood/serum- quantities,.They  generated  a specific  kind of pad alias Q  pad having unsaturated strips for the   determination of the  serum markers.These pads are requiredto be applied for a minimum of 4 hrs for the unsaturated strips to pick up the quantities.This is particularly of use for women  seeking infertility treatment with , no access .Furtherthere  observations were that these pads were good enough for determination of some steroid hormones normally evaluated  in  serum while HbA1c from venous blood both and in there multiple  asssessments they found concordance of HbA1cand these hormones.The only disadvantage was with menstrual cycle having lesser quantities at that  time  for  instance estradiol(E2) quantitiewhich might fall below the minimalaccepted limits of the range of test Otherwise it might be of cons use in infertile women with no access to medical facilities/cost factor/fear of pricks for facilitating early access for assisted reproductive technology(ART)once they have their day 2 values assessed besides even in invitro fertilization(IVF) lesser pricks needed .This needs to be further pursued as even  in women with   Polycystic ovary women syndrome (PCOS)  one can perform other tests needed further. 

Key Words-Menstrual effluent; HbA1c ;FSH;LH; AMH; cholesterol;CRPtesting


Innovative utilization of menstrual blood for determination of HbA1c, FSH, LH, AMH cholesterol,CRP quantitiesin infertile women with no access to medical facilities/cost factor/fear of pricks for facilitating early access for assisted reproductive technology(ART)-advantages of simultaneous testing of ones needing blood/serum- A Short Communication

Introduction

Routine blood evaluation monitors metabolic markers for  instance hemoglobin A1c (HbA1c), thyroid hormones, as well as a variation of necessary nutrients to aid in isolating early signs of disease risk, prescribing preventive care, as well as follow the manner treatments affected systemic health. Pertaining  to the women’s reproductive healthcare, clinicians determine blood quantities of crucial hormones correlated with fertility when screening for disorders for  instance polycystic ovary syndrome(PCOS), ovarian insufficiency(POI), along  with thyroid disorders (1, 2). Intrapopulation variation in serum hormone quantities are impacted by various factors, inclusive off age, caloric consumption, in addition to physical activity quantities (3). Standard practice for hormone determination depends on blood specimens acquired  via venipuncture, an approach having requirement for assistance from medical personnel along  with might result  in physical as well as emotional discomfort for the patient. Venipuncture methodologies stimulate  physiological stress reactions correlated with the   prediction of pain, despite repeated exposures (4). Despite at-home testing possess the capacity of escalating  healthcare accessibility, the acquisition of venipuncture blood samples at home usually needs particular processing, storage, in addition to temperature- regulated, speeded up transportation (5).Akin storage along  with transport restrictions influence reproductive hormone asssessment in noninvasive alternative samples, for  instance saliva in addition to urine (3). Sequentially, women usually   encounter significant hurdles in receiving fertility specialist consultations as well as reproductive hormone asssessment, emphasizing the need for expanding accessibility to these tests (6). Recently, fingerstick sampling via dried blood spot (DBS) has been  asssessed in  the form of a more convenient along  with cheaper alternative to a venous blood draw for controlling of HbA1c in addition to hormone quantities (7). Dried blood spot sampling conserves blood samples, enabling patients to self-collect specimens without needing to travel to a doctor’s office (5, 8). Blood is collected on filter paper, followed by the drying of the samples which  are shipped to a clinical laboratory for asssessment. Nevertheless, despite fingerstick blood sampling with DBS takes care of  certain of the logistical   hurdles  correlated with venipuncture, plethora of individuals are still not  comfortable with the self delivery of a fingerstick test in view of the plausible pain as well as soreness. Asssessment of physiological along  with psychological stress reactions poses a hurdle  regarding the properties of fingerstick in  the form of essentially  ‘‘less invasive’’ in contrast to  venipuncture, since participants’ stress reactions to fingerstick were akin  to (as well as for certain measures greater than) their reaction to venipuncture (9). Conversely, venipuncture or fingerstick estimation  by blood sampling, menstrual effluent presents a fully noninvasive, passively collected biological sample for biomarker monitoring. Menstrual effluent comprises of whole blood, vaginal fluids, as well as tissues shed from the endometrial lining in reaction to hormonal signaling (10). Although its possesses a complicated constitution along  with proinflammatory molecular signature (11, 12), recent studies have revealed an intricate  association   amongst menstrual as well as peripheral blood for inflammatory biomarkers (13),

 

Recently, Nasseri et al.[14], published an article entitled’’ Concordance of haemoglobin A1c (HbA1c ) and reproductive hormone levels in menstrual and    venous blood’, where they  revealed the approach  of  utilization of menstrual effluent along  with  a dried blood spot(DBS) in  a particularly  designed  pad- the Q pad-possessing unsaturated stripsn  for the   determination( whichcheckedeon 3-4 h of use)  of the  serum markers with the utilization of standard  laboratory methodologies in addition to  non invasive approaches .This methodology was  first displayed in 1989[15], as well as subsequentlyit has been an attractive ;albeit   minimally used for accumulating significant knowledge   in reference to ovarian working. Menstrual effluent gets constituted of  whole blood as well as vaginal fluids in addition to endometrial tissues[16], along  with the Q pad might be  utilized  for the  estimation of  both the markers where whole blood is the requirement for  instance HbA1c  quantities as well as the ones requiring serum for  instance follicle stimulating  hormone (FSH), Luteinizing hormone(LH) in addition to antimullerian hormone (AMH) quantities along  with other steroid hormone quantities. Earlier studies   had illustrated a greater association amongst menstrual blood as well as peripheral blood determination of HbA1c[17] quantities, FSH quantities, lipoprotein quantities in addition to quantities of other markers[1] as well as cholesterol, in addition to high-sensitivity C-reactive protein[18]. The association amongst menstrual DBS  evaluation along  with serum in this particular  study is good as well as the researchers have  paid attention with reference to asssessment of    the actions of the   different vaginal contaminations in  the form of the actions of the semen, vaginal medicines,urine in addition to others with just  the  contamination with faeces  having an effect. Despite,this is not any innovative  strategy along  with other studies   have performed the asssessment of its  applicability,this portrays the advantages of being  a prospective controlled   study of significance.

Figure 1: Courtesyref no-14-Stability of menstrual dried blood spot (DBS) samples was assayed by testing Q-Pad samples from three participants over a time course of 0–53 days for hemoglobin A1c (HbA1c) analysis and 0–15 days for hormone analysis. Graphs depict the percent difference from the DBS sample measurement on day 0. (B) Mean HbA1c and hormone levels in Q-Pad and matching venipuncture samples were compared for participants who collected menstrual samples on days 1, 2, or 3–5 of their period. Data are presented as the mean ± SD. Differences between timepoints were not significant (two-way ANOVA, P>.05). AMH = anti-müllerian hormone; HbA1c = hemoglobin  A1c; FSH = follicle-stimulating hormone; LH = luteinizing hormone; TSH = thyroid stimulating hormone.

Figure 2: Courtesyref no-14- (A) Deming linear regression for analyte measurements in menstrual blood (Q-Pad sample) vs. conventional blood draw. The gray region indicates the reference range of the analyte for healthy populations aged 18–45 years. Follicle-stimulating hormone (FSH) and LH reference ranges provided for early-follicular phase. (B) Pearson linear correlation for Q-Pad and venipuncture samples vs. subject age. The gray region indicates the reference ranges for healthy populations. AMH = anti-müllerian hormone; HbA1c = hemoglobin A1c; FSH = follicle-stimulating hormone; LH = luteinizing hormone; TSH = thyroid stimulating hormone; WB = whole blood.

 

The capacity of the patients  in collecting  the specimen is of benefit at their own house in case of transportation to  the laboratory was not feasible in view of no accessibility along  with availability for treatment was complex. Additionally, no stress encountered in collecting  the specimen would escalate the probability of compliance doing the same for the  patients for  instance adolescents,ii) the ones having fear for the needle pricks  iii)or full women categorized unsuitable for venipuncture . Nevertheless non invasive approaches continued   to be  promising subsequent to over   30yrs of work. The  explaination offered was   the reduction of precision of the markers having lesser quantities at the time of menstrual cycle for  instance estradiol(E2) quantities.

However,this  methodology would be having requirement for evaluation in  the  real world population .This study displayed approximately 25%of patients who gave consent failed to finish their taking part prior to attaining the samples, which has been revealed to be   in  the form of restriction  of this study .Of greater significance  was that of the samples estimated ,11-20%did not yield any outcomes in view of problems encountered  for  instance unsaturated strips, contamination with faeces,or  at the time of collecting serum sample there were reduction in  the values much lesser in contrast to  test range.As per Nasseri et al.[1],this occurred from patients problems.Asper their views requirement for taking  into account sufficient proper directions   accompanied by   correction of   medical  lapses.This extra botheration for the  practitioners would need assessment.

 

In view of maximum women going through evaluation for infertility, the earlier assessment is inclusive of determination of FSH, LH, AMH, in addition to E2quantities usuallyon  the day 2-4 of the menstrual cycle, therefore the estimation of these markers in  the menstrual effluent might work ideally. Addition of AMH would aid in fulfilling  the total assessment of the ovarian reserve.This non invasive   approach looks attractive;  since it aids in evaluating large chunk of women regarding their  plausibility for fertility   once  seeking conception giving reproductive freedom. On requirement for greater assessment these might be pacily achieved  by the reproductive endocrinologists for taking precise decision.

 

Conclusions

This investigational  modality would escalate the accessibility  of  care provision  to underprivileged women / from lesser socioeconomic strata, difficulty in obtaining transportation, care for children or laboratory having phlebotomy facilities placed distantly in addition to this would be particularly advantageous for the  initiatial asssessment of ovarian reserve. Furthermore ,it might be aiding in  amelioration of minimum of venipunctures at the time of invitro fertilization(IVF) treatment cycles.

This kind of  methodology needs to be  encouraged in reference to generation for  the improvement  of  quality of life (QOL) of these women  considerably[19].

 

References

1. Wheeler MJ.The measurement of LH, FSH, and prolactin. Methods Mol Biol  2013;1065:105-16.

2.  Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update 2014;20:688–701.

3. Gildner TE. Reproductive hormone measurement from minimally invasive sample types: methodological considerations and anthropological importance. Am J Hum Biol 2021;33:e23535. 4.

4.  Weckesser LJ, Plessow F, Pilhatsch M, Muehlhan M, Kirschbaum C, Miller R. Do venepuncture procedures induce cortisol responses? A review, study, and synthesis for stress research [study]. Psychoneuroendocrinology 2014; 46:88–99.

5. Freeman JD, Rosman LM, Ratcliff JD, Strickland PT, Graham DR, Silbergeld EK. State of the science in dried blood spots. Clin Chem 2018; 64:656–79.

6. Worthington AK, Burke EE, Shirazi TN, Leahy C. US women’s perceptions and acceptance of new reproductive health technologies. Womens Health Rep 2020;1:402–12.

7. Burke EE, Beqaj S, Douglas NC, Luo R. Concordance of fingerstick and venipuncture sampling for fertility hormones. Obstet Gynecol 2019;133:343–8.

8. McDade TW, Woodruff TK, Huang YY, Funk WE, Prewitt M, Kondapalli L, et al. Quantification of anti-Mullerian hormone (AMH) in dried blood spots: € validation of a minimally invasive method for assessing ovarian reserve. Hum Reprod 2012;27:2503–8.

9.  Lorenz TK. Autonomic, endocrine, and psychological stress responses to different forms of blood draw. PLOS ONE 2021;16:e0257110.

10. Yang H, Zhou B, Prinz M, Siegel D. Proteomic analysis of menstrual blood. Mol Cell Proteomics 2012;11:1024–35.

11. Crona Guterstam Y, Strunz B, Ivarsson MA, Zimmer C, Melin AS, Jonasson AF, et al. The cytokine profile of menstrual blood. Acta Obstet Gynecol Scand 2021;100:339–46.

12. Naseri S, Rosenberg-Hasson Y, Maecker HT, Avrutsky MI, Blumenthal PD. A cross-sectional study comparing the inflammatory profile of menstrual effluent vs. peripheral blood. Health Sci Rep 2023;6:e1038.

13. da Silva CM, Vilac¸a Belo A, Passos Andrade S, Peixoto Campos P, Cristina Franc¸a Ferreira M, Lopes da Silva-Filho A, et al. Identification of local angiogenic and inflammatory markers in the menstrual blood of women with endometriosis. Biomed Pharmacother 2014;68:899–904. 

14. Nasseri S,Avrutsky M,Capati C,Desai D,A R Blumenthal P. Concordance of haemoglobin A1c (HbA1c ) and reproductive hormone levels in menstrual andvenous blood.FS Rep2024;5:33-9.

15. ZhouJP, Fraser JS,Caterson I, Grivas A,McCarson G,Norman D,etal. reproductive hormones in menstrual blood. J Clin Endocrinol Metab   2007;92(8):3068-75.

16. YangH, ZhouB,PrinzM,SiegelD. proteomic -analysis of menstrual blood.  Mol CellProteomics 2012; 11: 1024-35.  

17. Nasseri S,Brewster RCL, Blumenthal P.Novel use of    menstrual blood for monitoring theglycaemic  control  in   patients with diabetes:proof of concept study. BMJSex Reprod Health 2022;48:123-7.

18. Naseri S, Lerma K, Blumenthal P. Comparative assessment of serum versus menstrual blood for diagnostic purposes: a pilot study. J Clin Lab Med 2019;4.

19. Detti L,Gibbson WE. Hormonal testing in menstrual blood  enhances reproductive freedom. FS Rep2024;5:13-13.

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