An interplay of Progesterone, Leukemia Inhibitor Factor and Interleukin-6 in the window of implantation; Impact on fertility

Rabiya Ali; Ali R; Taseer Ahmed Khan; Ahmed Khan T; Gul H; Hina Gul; Rehana Rehman; Rehman R

doi:10.1016/j.cyto.2023.156332

An interplay of Progesterone, Leukemia Inhibitor Factor and Interleukin-6 in the window of implantation; Impact on fertility

Rabiya Ali, Ali R, Taseer Ahmed Khan, Ahmed Khan T, Gul H, Hina Gul, Rehana Rehman, Rehman R

Cytokine · 2023 · vol. 170 , pp. 156332 · doi:10.1016/j.cyto.2023.156332 · PMID:37586287

other OA: green CC-BY-NC-ND-4.0

🔓 Open OA copy Full text JSON View on PubMed View at publisher

⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Fertile women had higher progesterone, LIF, IL6, and FSH/LH ratio than infertile groups, with progesterone positively correlating with LIF and IL6, suggesting its role in implantation.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-15 · read from full text ⓘ

This case-control study (Oct 2020–Mar 2023) measured serum estradiol, progesterone, leukemia inhibitory factor (LIF), and interleukin-6 (IL6) by ELISA, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from records, comparing 177 fertile women with 135 infertile women across polycystic ovaries (PCOs), endometriosis, and unexplained infertility (Uex-IF). Fertile women had significantly higher progesterone, LIF, IL6, and a higher FSH/LH ratio, while many infertile participants with PCOs or Uex-IF had lower progesterone levels (still within reference range) and, in the Uex-IF subgroup, IL6 levels below the reference range. Within groups, LIF correlated positively with IL6 and with steroid hormones (and with LH in several strata), but the authors note that the exploration of low LIF in women with endometriosis requires further investigation. Relevance to endometriosis: endometriosis was one of the infertile comparison groups and showed relatively low LIF and altered LIF–IL6 and LIF–progesterone correlations, though endometriosis was not the primary focus of the study.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

BACKGROUND: The process of implantation is crucial for the initiation of conception and hence fertility. In addition to a number of factors, it is regulated by a cross talk of gonadotrophins [Luteinizing Hormone (LH), Follicle Stimulatory Hormone (FSH)], ovarian steroids [Estrogen (Et), Progesterone (Pt)] and cytokines [Leukemia inhibitory factor (LIF) and Interleukin 6 (IL6)]. These biomarkers are chief players of implantation. OBJECTIVE: We aimed to explore the role of gonadotrophins (LH, FSH, LH/FSH ratio), ovarian steroids (Et, Pt) and cytokines (LIF, IL6) in the implantation process. This aim was achieved by comparing these hormones and cytokines in the fertile and infertile groups [Polycystic ovaries (PCOs), endometriosis, unexplained infertility (Uex-IF)] and finding their association in all study groups. METHODS: A case control study conducted from October 2020-March 2023. A total of 135 infertile women (with PCOs, Uex-IF, and endometriosis) and 177 fertile women (matched for age and BMI) were selected. Levels of 'Et', 'Pt', 'LIF' and, 'IL6' were estimated using Enzyme Linked Immunosorbent Assay (ELISA). LH and FSH values were obtained from hospital desk records. The Independent Student'st-test was used to compare fertile and infertile groups. One-way ANOVA test was used to compare more than two groups, and Pearson's chi-square (χ2) test was employed to compare percentages of variables. Pearson correlation analysis was performed to assess the associations and correlations. A p value < 0.05 was considered statistically significant. RESULTS: Significantly higher levels of LIF and IL6 were observed in fertile women compared to infertile women. Pt levels were significantly greater in the fertile group than in the infertile group. The FSH/LH ratio was significantly higher in the fertile group. Among infertile women, PCOs (71%) and Uex-IF (91%) exhibited lower Pt levels than the fertile controls (p < 0.01), but these levels remained within the reference range (RR). Among the fertile group (81%), levels of LIF within the RR were significantly higher compared to those with Uex-IF (49%) and females with endometriosis (37%). Moreover, the highest number of participants (57%) with Uex-IF exhibited IL6 levels significantly below the RR in comparison to the fertile group and infertile groups (PCOS and endometriosis). However, lower levels of IL6 were observed in women with Uex-IF. In the control group, LIF exhibited a significant positive correlation with IL6 (r = 0.370), Pt (r = 0.496), Et (r = 0.403), and LH (r = 0.428). Among women with PCOs, LIF showed a significant positive correlation with IL6 (r = 0.443), Pt (r = 0.607), and LH (r = 0.472). In cases of Uex-IF, LIF demonstrated a significant positive correlation with IL6 (r = 0.727). Females with endometriosis displayed a significant positive correlation between LIF and IL6 (r = 0.535) as well as Pt (r = 0.605). In fertile women, a positive correlation was observed between LH and IL6 (r = 0.197, p = 0.009), LIF (r = 0.428, p = 0.000), Pt (r = 0.238, p = 0.001), and Et (r = 0.356, p = 0.000). Furthermore, a positive correlation was found between LH and LIF (r = 0.472, p = 0.000) in women with PCOs. CONCLUSION: Elevated levels of Pt were found to increase the production of LIF in fertile females. However, infertile females with PCOs and Uex-IF exhibited deficient levels of Pt, supporting its role as a biomarker for successful implantation in infertile women. These females showed decreased levels of gonadotropins as well as reduced LH/FSH ratio and diminished secretion of receptivity marker LIF, in addition to reduced Pt secretion. This suggests that reduced gonadotropin levels contribute to a lower LH/FSH ratio, resulting in decreased Pt secretion and ultimately leading to low levels of LIF, thereby causing impaired implantation in women with PCOs and Uex-IF. The exploration of low levels of LIF in patients with endometriosis requires further investigation. The significantly low levels of IL6 in the Uex-IF group elucidate the role of this cytokine in association with decreased Pt and LIF synthesis within this group.

Full text 4,777 characters · extracted from oa-html · 5 sections · click to expand

Abstract

Background: The process of implantation is crucial for the initiation of conception and hence fertility. In addition to a number of factors, it is regulated by a cross talk of gonadotrophins [Luteinizing Hormone (LH), Follicle Stimulatory Hormone (FSH)], ovarian steroids [Estrogen (Et), Progesterone (Pt)] and cytokines [Leukemia inhibitory factor (LIF) and Interleukin 6 (IL6)]. These biomarkers are chief players of implantation.

Objective

We aimed to explore the role of gonadotrophins (LH, FSH, LH/FSH ratio), ovarian steroids (Et, Pt) and cytokines (LIF, IL6) in the implantation process. This aim was achieved by comparing these hormones and cytokines in the fertile and infertile groups [Polycystic ovaries (PCOs), endometriosis, unexplained infertility (Uex-IF)] and finding their association in all study groups.

Methods

A case control study conducted from October 2020-March 2023. A total of 135 infertile women (with PCOs, Uex-IF, and endometriosis) and 177 fertile women (matched for age and BMI) were selected. Levels of 'Et', 'Pt', 'LIF' and, 'IL6' were estimated using Enzyme Linked Immunosorbent Assay (ELISA). LH and FSH values were obtained from hospital desk records. The Independent Student'st-test was used to compare fertile and infertile groups. One-way ANOVA test was used to compare more than two groups, and Pearson's chi-square (χ2) test was employed to compare percentages of variables. Pearson correlation analysis was performed to assess the associations and correlations. A p value < 0.05 was considered statistically significant.

Results

Significantly higher levels of LIF and IL6 were observed in fertile women compared to infertile women. Pt levels were significantly greater in the fertile group than in the infertile group. The FSH/LH ratio was significantly higher in the fertile group. Among infertile women, PCOs (71%) and Uex-IF (91%) exhibited lower Pt levels than the fertile controls (p < 0.01), but these levels remained within the reference range (RR). Among the fertile group (81%), levels of LIF within the RR were significantly higher compared to those with Uex-IF (49%) and females with endometriosis (37%). Moreover, the highest number of participants (57%) with Uex-IF exhibited IL6 levels significantly below the RR in comparison to the fertile group and infertile groups (PCOS and endometriosis). However, lower levels of IL6 were observed in women with Uex-IF. In the control group, LIF exhibited a significant positive correlation with IL6 (r = 0.370), Pt (r = 0.496), Et (r = 0.403), and LH (r = 0.428). Among women with PCOs, LIF showed a significant positive correlation with IL6 (r = 0.443), Pt (r = 0.607), and LH (r = 0.472). In cases of Uex-IF, LIF demonstrated a significant positive correlation with IL6 (r = 0.727). Females with endometriosis displayed a significant positive correlation between LIF and IL6 (r = 0.535) as well as Pt (r = 0.605). In fertile women, a positive correlation was observed between LH and IL6 (r = 0.197, p = 0.009), LIF (r = 0.428, p = 0.000), Pt (r = 0.238, p = 0.001), and Et (r = 0.356, p = 0.000). Furthermore, a positive correlation was found between LH and LIF (r = 0.472, p = 0.000) in women with PCOs.

Conclusion

Elevated levels of Pt were found to increase the production of LIF in fertile females. However, infertile females with PCOs and Uex-IF exhibited deficient levels of Pt, supporting its role as a biomarker for successful implantation in infertile women. These females showed decreased levels of gonadotropins as well as reduced LH/FSH ratio and diminished secretion of receptivity marker LIF, in addition to reduced Pt secretion. This suggests that reduced gonadotropin levels contribute to a lower LH/FSH ratio, resulting in decreased Pt secretion and ultimately leading to low levels of LIF, thereby causing impaired implantation in women with PCOs and Uex-IF. The exploration of low levels of LIF in patients with endometriosis requires further investigation. The significantly low levels of IL6 in the Uex-IF group elucidate the role of this cytokine in association with decreased Pt and LIF synthesis within this group. Comments Issue and pagination are not provided by the author/publisher. Publication (Name of Journal) Cytokine DOI https://doi.org/10.1016/j.cyto.2023.156332 Recommended Citation Ali, R., Khan, T. A., Gul, H., Rehman, R. (2023). An interplay of progesterone, leukemia inhibitor factor and interleukin-6 in the window of implantation; impact on fertility. Cytokine, 170. Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/1024

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-html ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisinfertility

MeSH descriptors

Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation Embryo Implantation

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

Source provenance

europepmc: last seen: 2026-08-09T06:10:49.860119+00:00
pubmed: last seen: 2026-08-09T06:09:44.518668+00:00
unpaywall: last seen: 2026-05-14T19:30:52.867331+00:00

License: CC-BY-NC-ND-4.0 · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine