Impact of Donor-Recipient Sex-Mismatch on Graft Failure in Osteochondral Allograft Procedures: A Systematic Review

Abstract

Background:

While midterm outcomes of donor-recipient sex-mismatch have been reported after knee osteochondral allograft procedures, no studies have been conducted to report on all available literature.

Purpose:

To investigate whether sex-mismatch between donor and recipient influences graft survival in studies evaluating knee OCA surgery.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Three databases (PubMed, Embase, and Cochrane) were searched for published studies evaluating donor sex-specific outcomes in human subjects. Studies were included regardless of the level of evidence. All studies were manually screened, followed by a full-text review and data extraction. All outcome measures reported in studies were recorded. The extracted data were reported as descriptive statistics. A risk-of-bias assessment was also conducted for each identified study.

Results:

Of 140 full-text articles screened, 4 articles were included in this analysis. Of these, 1 study concluded that a donor-recipient sex mismatch is a negative predictor of outcomes, while 3 studies (75%) found no difference in postoperative outcomes between donor-recipient pairs. Two studies analyzed individual sex pairings (eg, female-to-male pairing), and 1 found lower survival in male-to-female grafts. A failure rate of 14% OCA was observed across 973 knees—including 514 male recipients (53%) and 459 female recipients (47%). At baseline, concomitant tibial tubercle osteotomy was more common in sex-mismatched pairing (14% compared with 8%), and concomitant high tibial osteotomy in sex-matched pairing (9% compared with 4%). Other adjuvant procedures and patient characteristics were comparable. Failure rate for donor-recipient sex-matched and sex-mismatched cohorts was 15% and 13%, respectively.

Conclusion:

This study assessed the current literature to determine the role of donor-recipient sex pairing in the outcomes of OCA transplantation. Only 1 study (25%) concluded a significant difference in graft failure among sex-matched and mismatched cohorts. A principal concern of this review is that only 4 studies report data on donor-recipient sex pairings. Only one-fifth of all patients received a female donor graft, limiting the ability to draw conclusions about subgroups. Graft failure across all studies was comparable between sex-matched and sex-mismatched cohorts. This study supports current graft-matching practices, primarily based on size and anatomy, without sex matching.

Keywords

allografts articular cartilage resurfacing knee

Multiple treatment options exist for osteochondral lesions, and osteochondral autograft or allograft transplantation is an accepted option in certain cases. For lesions >2 cm² that involve subchondral bone, osteochondral allograft transplantation (OCA) may be indicated, as it restores bone and cartilage with mature hyaline tissue and reduces the risk of donor-site morbidity.^5,15,16 Although OCA is effective for large lesions, reoperation may be indicated in a subset of patients.

The negative outcomes associated with OCA, such as graft integration failure, reoperation, and persistent pain or stiffness, have been well reported in the literature.^3,4 This has prompted the identification of modifiable and nonmodifiable risk factors associated with adverse outcomes. Among the ones currently reported in the literature are increased body mass index (BMI), diagnosis of osteoarthritis, and bipolar chondral defects.^1,6,7 OCA provides clinical benefits that often delay or avert conversion to arthroplasty.

Current tissue bank protocols consider size and anatomy when matching donor grafts to the recipient for OCA transplantation.¹⁸ The patient's condyle size and radius of curvature direct certain matches. Fewer female donors are available due to lower rates of fatal trauma compared with male donors, and female donors are often unsuitable for male recipients due to graft size mismatch.^6,8,14 Recent literature has reported donor graft characteristics (eg, donor sex, donor age, and graft storage time) that may influence mid- and long-term graft survival. It has been proposed that an association may exist between donor-recipient sex-mismatch and OCA transplantation failure as a result of immunologic response or gross anatomic differences. Proposed mechanisms include immune recruitment driven by sex-specific differences in hormone composition or by sex-specific minor histocompatibility complex antigens located on the Y chromosome.^8,14 This systematic review aims to report on all peer-reviewed evidence assessing the role of donor-recipient sex-mismatch on OCA graft survival and highlight gaps in the literature.

Methods

Study Design

A systematic search was conducted in PubMed, EMBASE, and the Cochrane Trials database, following the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. This study was registered on PROSPERO (International Prospective Register of Systematic Reviews), an international prospective register of systematic reviews (CRD420251068509). The databases were searched to identify original peer-reviewed studies reporting on outcomes of knee OCA transplantation procedures. The individual search strategies are reported in the supplemental information. Database searches were run on June 6, 2025. Studies were imported to the online program, Rayyan.ai (Cambridge), where duplicates were manually removed by 1 reviewer (M.B.). The titles and abstracts of all identified articles were screened independently by 3 reviewers (M.B., N.S., or I.P.). After the initial screening, discrepancies among the reviewers were discussed and resolved by the primary author (M.B.) based on consensus among reviewers. Full-text articles were retrieved, and full-text screening was conducted in the same format as the initial screening described above. The results of the PRISMA search are presented in Figure 1.

Figure 1.

Summary of study inclusion using the PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Eligibility Criteria

Studies published in English reporting on graft-related outcomes after knee OCA procedures were included. The inclusion criteria were designed to capture all relevant articles, with the main limiting criterion that graft donor sex must be reported in relation to graft outcomes. Study types excluded from this review include systematic reviews, case reports, animal studies, editorials, narrative reviews, and cadaveric studies. In addition, studies that did not report graft donor and recipient sex, graft outcomes, or were not focused on OCA procedures were excluded.

Data Extraction

The following data, if reported, were extracted from each study: total number of patients, recipient and donor sex, age at surgery, BMI, sex-match groups (male-to-male, female-to-female, male-to-female, and female-to-male), graft type, surgical technique, laterality of reconstruction, defect location and diameter, presence of concomitant procedures or pathology, functional outcome scores (International Knee Documentation Committee, knee injury and osteoarthritis outcome scores [KOOS]; visual analog scale [VAS]), graft survival and failure rates, return-to-sport (RTS) rates, imaging modality used to assess outcomes, whether sex-mismatch was evaluated as a primary or secondary outcome, statistical methods used, covariates controlled for, study limitations, and key findings.

Quality-of-Bias Assessment

A quality-of-bias assessment was performed using the MINORS (methodological index for nonrandomized studies) scoring instrument. Each study was evaluated based on 12 criteria with an assigned score of 0, 1, or 2 for each criterion. A score of 2 indicates adequate reporting of the item, 1 indicates the item is reported, but inadequate, and 0 indicates the item is not reported. The MINORS ideal score is 24 for comparison studies. For this review, scores >19 are considered good, scores from 16 to 19 are considered fair, and scores <16 are considered poor.

A meta-analysis was determined not to be appropriate in this review. This is due to heterogeneity in studies, outlined by the population of interest, intervention, follow-up lengths, and outcome definitions. The small number of studies identified further restricts the ability to pool results.

Results

We identified 4 studies published between 2012 and 2025 that report OCA knee graft outcomes during treatment in 973 patients. The results of the systematic search are reported in Figure 1. The search strategy was applied to 3 databases and yielded 2425 articles. Title and abstract screening was performed on 1426 studies, resulting in 140 for full-text review. Most studies (121/140 [86%]) were excluded during full-text review because they failed to report donor-graft sex in relation to graft outcomes. Of the 4 studies identified, 2 studies^8,14 reported on graft survival outcomes in relation to the individual donor-recipient sex matching (ie, male donor to female recipient), while 2 studies^10,18 reported on outcomes in relation to donor-recipient sex-matched or mismatched without further differentiating.

Quality-of-Bias Assessment

The methodological quality of the studies in this review met the criteria for fair (50%) or good (50%) quality, with scores ranging from 19 to 21 out of 24 possible points. All studies adequately stated clear aims with appropriate endpoints and satisfactory multivariate analyses adjusting for covariates, but were limited by a lack of blinding or by failure to report blinding. The studies used retrospective or registry-based designs. Only 1 study (25%) adequately performed a prospective calculation of the necessary study size.⁸ The majority of papers (75%) adequately reported the mean follow-up time for reporting graft outcomes, with 1 study reporting a minimum of 1-year follow-up. The breakdown of individual MINORs scoring for each paper can be found in the supplemental information.

Patient Characteristics

Four studies^8,10,14,18 comprised 973 knees, with 514 male recipients (53%) and 459 female recipients (47%) (Table 1). The mean age across all studies ranged from 31.2 to 38.8 years, with an age range of 12 to 69 years. The percentage of sex-matched graft-donor procedures was higher than the percentage of sex-mismatched graft-donor procedures in every study. The percentage of sex-matched procedures ranged from 58% to 66% across all studies, while the percentage of sex-mismatched procedures ranged from 34% to 42%.

Table 1

Study Characteristics ^a

Author (Year)	Study Design	LoE	Follow-up, Years	No. of Patients	Mean Age at Surgery, Years	Sex- Matched	Male → Male	Female → Female	Sex- Mismatched	Male → Female	Female → Male
Hevesi et al⁸ (2025)	Cohort	3	5.4 ± 2.7	372	31.2 ± 9.8	217 (58)	157 (72)	60 (28)	155 (42)	139 (90)	16 (10)
Lott et al¹⁰ (2025)	Cohort	4	4.8 ± 2	285	32.4 ± 11.1	189 (66)	147 (78)	42 (22)	96 (34)	76 (79)	20 (21)
Merkely et al¹⁴ (2022)	Cohort	3	3.3 ± 1.2	154	34.7 ± 10.7	102 (66)	71 (70)	31 (30)	52 (34)	46 (88)	6 (12)
Williams et al¹⁸ (2025)	Cohort	3	≥1 ^b	162	38.8 ± 12.6	105 (65)	90 (86)	15 (14)	57 (35)	50 (88)	7 (12)
			Total	973		613 (63)	465 (76)	148 (24)	360 (37)	311 (86)	49 (14)

Data are presented as mean ± SD or n (%). Sex-matched and sex-mismatched percentages were calculated using the total number of patients in each study as the denominator, and subgroup percentages (Male→Male, Female→Female, Male→Female, Female→Male) were calculated relative to the total number of sex-matched or sex-mismatched patients. LoE, level of evidence.

The study included patients with ≥85 months of follow-up, with a minimum of 1-year follow-up; the mean and standard deviation of the follow-up were not reported.

Patient-specific characteristics are presented in Table 2. The reported BMI values were comparable across all studies, with the sex-matched cohort BMI range of 27.2 to 28.8 kg/m² and the sex-mismatched cohort range of 26.7 to 27.7. One study⁸ did not report overall BMI values for sex-matched or sex-mismatched groups but provided BMI results for specific cohorts, ranging from 24.8 (female-to-female group) to 27.9 (male-to-male group). Overall smoking rates were 7% of the total, with the same rate when stratifying based on sex-matched and mismatched cohorts. One study¹⁰ did report significantly different baseline levels of smoking status, with the sex-matched cohort having higher levels at baseline (11% compared to 3%). Sex-matched and sex-mismatched groups underwent comparable rates of concomitant procedures, with the largest difference observed in the rates of tibial tubercle osteotomy (TTO) and high tibial osteotomy (HTO). TTO was performed less in the sex-matched cohort (8%) compared with the sex-mismatched cohort (14%), while HTO was more common in the sex-matched group (9%) compared with the sex-mismatched group (4%). This was supported by the individual study results with 2 studies^8,10 reporting a significantly higher frequency of TTO in the sex-mismatched group, and 2 studies^10,14 reporting HTO rates significantly higher in the sex-matched cohort.

Table 2

Patient Characteristics and Concomitant Procedures Stratified by Donor-Recipient Sex-Match Status ^a

Donor-Recipient Sex-Matching Cohorts by Study (Year)	BMI	Smoker	Concomitant Procedures
Donor-Recipient Sex-Matching Cohorts by Study (Year)	BMI	Smoker	HTO	TTO	DFO	ACLR	MAT	Other
Hevesi et al⁸ (2025)
Matched	-	14 (6)	22 (10)	11 (5)	10 (5)	14 (6) ^b	93 (43)	BMAC: 21 (10); PRP: 4 (2); MS: 16 (7)
Mismatched	-	13 (8)	8 (5)	17 (11)	6 (4)	5 (3) ^b	60 (39)	BMAC: 23 (15); PRP: 3 (2); MS: 9 (6); ACI: 2 (1)
Lott et al¹⁰ (2025)
Matched	27.2 ± 5.3	20 (11)	21 (11)	25 (13)	4 (2)	12 (6)	13 (7)	Multiple plugs: 18 (10)
Mismatched	26.7 ± 5.3	3 (3)	4 (4)	25 (26)	6 (6)	3 (3)	3 (3)	Multiple plugs: 5 (5)
Merkely et al¹⁴ (2022)
Matched	27.4 ± 4.6	3 (3)	11 (11)	11 (11)	1 (1)	2 (2)	3 (3)	-
Mismatched	27.4 ± 6.2	4 (8)	2 (4)	8 (15)	0 (0)	3 (6)	3 (6)	-
Williams et al¹⁸ (2025)
Matched	28.8 ± 4.9	-	3 (3)	2 (2)	5 (5)	7 (7) ^c	0 (0)	Bipolar OCA: 48 (46)
Mismatched	27.7 ± 5.4	-	2 (4)	0 (0)	2 (4)	3 (5) ^c	0 (0)	Bipolar OCA: 23 (40)
Overall		57 (7) ^d	73 (8)	99 (10)	34 (3)	49 (5)	175 (18)
Matched		37 (7) ^d	57 (9)	49 (8)	20 (3)	35 (6)	109 (18)
Mismatched		20 (7) ^d	16 (4)	50 (14)	14 (4)	14 (4)	66 (18)

Data are presented as mean ± SD or n (%). Percentages are calculated relative to the total number of sex-matched or sex-mismatched patients in each study. Sex-specific donor-recipient match and mismatch data are provided in the supplementary material. Baseline characteristics (BMI, smoking status, and concomitant procedures) are not reported in relation to graft failure outcomes. Dashes (-) indicate that data are not reported. ACI, autologous chondrocyte implantation; ACLR, anterior cruciate ligament reconstruction; BMAC, bone marrow aspirate concentrate; BMI, body mass index; DFO, distal femoral osteotomy; HTO, high tibial osteotomy; MAT, meniscal allograft transplantation; MS, microfracture stimulation; OCA, osteochondral allograft; PRP, platelet-rich plasma; TTO, tibial tubercle osteotomy.

Ligament repair or reconstruction, not limited to ACLR.

Reporting number of ACL repairs.

Percentage calculated with total cohort numbers excluding Williams et al¹⁸ because of unreported values.

Two studies^10,14 report on the anatomical distribution of defect locations (Supplemental Table S3). Sex-matched and sex-mismatched cohorts were represented across all compartments. The medial tibiofemoral compartment was the most common site of defect (187 knees, 43%). This was followed by the patellofemoral (144 knees, 33%) and lateral tibiofemoral (101 knees, 24%) lesions.

Long-Term OCA Outcomes

The definitions of graft failure were similar across the included studies. All considered revision OCA surgery or conversion to knee arthroplasty as a failure. Studies by Merkely et al¹⁴ and Lott et al¹⁰ also identified failure by subchondral collapse on postoperative magnetic resonance imaging (MRI) or arthroscopy. A detailed description of failure for each study is provided in Supplemental Table 4. The mean follow-up time was reported in 3 studies, ranging from 3.3 ± 1.2 years to 5.4 ± 2.7 years, with a minimum follow-up of 24 months.^8,10,14 The 1 study that did not report a mean follow-up had a minimum follow-up of 12 months.¹⁸

The combined failure rate was 14%, and the sex-matched (13%) and mismatched (15%) cohorts had similar rates (Table 3). Only 1 included study¹⁴ had data to support that a mismatch between donor and recipient sex has a negative effect on OCA overall survival after transplantation. This study found failure rates of 7% in sex-matched cases versus 21% in sex-mismatched cases and determined that patients in the sex-mismatched cohort had a 2.9-fold increased probability of failure at 5 years, after correcting for BMI, age, and graft size. The 5-year survival rates were relatively wide, with the highest observed in male-to-male donor-recipient pairs (94%), followed by female-to-female (91%) and female-to-male (84%). The lowest rate was reported at 64% for male-to-female grafting, with this group at a 2.6-fold increased risk of failure compared with other pairings. However, in this study, the small size of the female-to-male group (6 patients; 4% of the total study population) led to an underpowered subgroup analysis, limiting the ability to draw objective conclusions surrounding long-term OCA outcomes in this population. A second study¹⁰ found that the sex-mismatched cohort experienced failure at a faster rate than the sex-matched cohort, with no significant difference in the overall failure rate at 5-year follow-up. The mean time to failure for sex-matched and sex-mismatched cohorts was 864 days and 353 days, respectively. This study reported that, after adjusting for patient sex, VAS satisfaction, VAS pain, and KOOS, there were no significant differences in scores between patients receiving grafts from same-sex versus different-sex donors. RTS rates were also not found to be significantly different, with 65% for same-sex and 54% for different-sex donor recipients. For the remainder of the included studies, there were no significant differences in OCA graft survival between patients with sex-matched or sex-mismatched donor-graft recipient sex pairings.

Table 3

Graft Failure and Survival by Donor-Recipient Sex-Match ^a

Author (Year)	Overall Failure Rate	Sex-Matched Failure Rate, n (%)	Sex-Mismatched Failure Rate, n (%)	Graft Survival				Significant Findings
Author (Year)	Overall Failure Rate	Sex-Matched Failure Rate, n (%)	Sex-Mismatched Failure Rate, n (%)	Male → Male, %	Female → Female, %	Male → Female, %	Female → Male, %	Significant Findings
Hevesi et al⁸ (2025)	63 (17)	36 (17)	27 (17)	88	96	90	79	No difference in survival or reoperation rates
Lott et al¹⁰ (2025)	12 (6)	12 (6)	5 (5)	-	-	-	-	Sex-mismatched grafts failed sooner (353 vs 864 days)
Merkely et al¹⁴ (2022)	18 (12)	7 (7)	11 (21)	94	91	64	84	Lower 5-year survival (matched 92% vs mismatched 63%), 2.9× higher failure risk
Williams et al¹⁸ (2025)	38 (23)	26 (25)	12 (21)	-	-	-	-	No survival difference (matched 75% vs mismatched 79%)
Total	136 (14)	81 (13)	55 (15)

5-year graft survival is stratified by donor-recipient sex combinations where available. Dashes (-) indicate that data are not reported. Failure is based on a study-specific definition, included in the supplementary information. Percentages for overall failure are calculated based on the total number of patients within each study, and sex-matched and sex-mismatched failure rates are based on the total number of patients within each respective subgroup.

Risks Associated With Specific Sex-Pairings

Across all studies, the number of female graft donors and female-to-male donor/recipient groups was severely limited. Across all studies combined, there were 197 female donors out of 973 (20%). To further this point, across all studies combined, 49 female donor grafts were implanted in male recipient knees. This comprises only 5% of all OCA procedures included in this review.

Discussion

This study examined the outcomes of donor-recipient sex-mismatch on patients undergoing OCA in the knee. OCA is an important surgical procedure used to address relatively large and/or unstable osteochondral defects without the associated donor-site morbidity associated with osteochondral autograft transfer. To achieve optimal outcomes for patients, several studies have examined the role of donor-recipient sex matching in osteochondral allograft transplantation (OCA),^14,18 anterior cruciate ligament reconstruction,² and meniscal transplantation.¹¹ Our review of the literature concludes that there is no significant difference between long-term OCA outcomes between sex-matched and sex-mismatched donor-recipient pairings. However, these conclusions are drawn from only 4 studies, with data that underrepresent female donor tissues and male recipients of female donor tissue.

Our study included 973 knees that underwent OCA transplantation. Of these 973 procedures, only 197 female donor tissues were utilized (20%). Furthermore, a total of 49 female donor grafts were implanted in male recipient knees, comprising only 5% of all OCA procedures included in these studies. This lack of data surrounding female donor tissue severely underpowers subgroup analysis to draw meaningful conclusions regarding the effect that donor-recipient sex matching has on long-term OCA outcomes. Of interest, 1 study¹⁴ concluded that a mismatch between donor and recipient sex had a negative impact on OCA survival after transplantation. In this study, sex-matched OCA procedures had a failure rate of 7 out of 102 (7%) compared to sex-mismatched OCA procedures with a failure rate of 11/52 (21%). Their definitions of failure were similar to those of other included studies, considering removal or revision of the primary OCA, or conversion to any form of arthroplasty as failure. Of note, this study also deemed subchondral collapse of the transplant on postoperative MRI or second-look arthroscopy as a definition of failure, in line with one other study.¹⁴ This did not contribute to a higher overall reported failure rate when compared with other studies. Multiple mechanisms have been proposed to connect OCA failure to donor-recipient sex mismatch cohorts. These mechanisms include immunologic origins wherein adaptive immune cell activity, stimulated by differences in the hormonal environment or influenced by H-Y minor histocompatibility antigens, directly or indirectly prevent adequate OCA osteointegration.^12,13 While there are possible biological reasons why sex-mismatch could affect outcomes, current evidence does not show a strong or consistent impact.

For the remainder of the included studies, there were no significant differences in OCA graft survival between patients with sex-matched or sex-mismatched donor-graft recipient sex pairings. The other studies showed that factors such as BMI, graft size, and age had a stronger influence on outcomes than sex match, in line with previous reported literature.^9,17 These findings are consistent with how grafts are typically selected in clinical practice, based on size and anatomy rather than donor sex.

This study is not without limitations. A prominent limitation is the limited number of published studies reporting results of donor-recipient sex pairing in relation to OCA graft outcomes. Across all studies, there was a paucity of female donor grafts, resulting in underpowered subgroup analyses that severely limited the ability to draw definitive conclusions. In particular, the only study to report an association between sex-mismatching and decreased graft survival used only 37 female donor tissues (24% of the study population), and only 6 patients (4% of the study population) were male recipients of a female OCA donor.¹⁴ A meta-analysis could not be performed given the small number and heterogeneity of studies. Other limitations include a lack of long-term data, with the longest follow-up being 5.4 ± 2.7 years, and multiple confounders, such as graft size and defect location, not adequately accounted for. This review is also limited by the inclusion of retrospective studies, which inherently increase the risk of selection bias. There are currently no prospective studies or randomized controlled trials reporting on this topic. The focus on sex-pairing in OCA transplantation is relatively novel, as 75% of studies were published within the past 12 months at the time of this writing.

Conclusion

This study assessed the current literature to determine the role of donor-recipient sex pairing in the outcomes of OCA transplantation. Only 1 study (25%) concluded a significant difference in graft failure among sex-matched and mismatched cohorts. A principal concern of this review is that only 4 studies report data on donor-recipient sex pairings. Furthermore, only one-fifth of all patients received a female donor graft, limiting the conclusion of subgroups (eg, female-to-male pairing). Graft failure across all studies was comparable between sex-matched and sex-mismatched cohorts. This study supports current graft-matching practices. Prospective studies are necessary to further clarify the role of donor-recipient sex-pairing in OCA.

Supplemental Material

sj-docx-1-ojs-10.1177_23259671251407241 – Supplemental material for Impact of Donor-Recipient Sex-Mismatch on Graft Failure in Osteochondral Allograft Procedures: A Systematic Review

Supplemental material, sj-docx-1-ojs-10.1177_23259671251407241 for Impact of Donor-Recipient Sex-Mismatch on Graft Failure in Osteochondral Allograft Procedures: A Systematic Review by Michael Bartkoski, Noah Schnieders, Zachary Denton, Isabelle Pro, Sterre van den Anker, Matthew L. Vopat and Bryan G. Vopat in Orthopaedic Journal of Sports Medicine

Footnotes

Final revision submitted October 14, 2025; accepted November 4, 2025.

One or more of the authors has declared the following potential conflict of interest or source of funding: B.G.V. serves in consulting or advisory roles with Artelon and Stryker and holds equity or stock in Altior, Carbon 22, and Spinal Simplicity. All other authors declare no competing interests that could influence the data reported.

ORCID iDs

Michael Bartkoski

Sterre van den Anker

Supplemental Material

Supplemental material for this article is available at # supplementary-materials

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