Usage and cost-effectiveness of elective oocyte freezing: a retrospective observational study.

BACKGROUND: The previous model-based cost-effectiveness analyses regarding elective oocyte cryopreservation remained debatable, while the usage rate may influence the cost per live birth. The aim of this study is to disclose the usage and cost-effectiveness of the planned cryopreserved oocytes after oocyte thawing in real-world situations. METHODS: This was a retrospective single-center observational study. Women who electively cryopreserved oocytes and returned to thaw the oocytes were categorized as thawed group. The oocytes were fertilized at our center and the sperm samples for each individual was retrieved from their respective husbands. Clinical outcomes were traced and the cumulative live birth rate per thawed case was calculated. The costs from oocyte freezing cycles to oocyte thawing, and embryo transfer cycles were accordingly estimated. The cumulative cost per live birth was defined by the cumulative cost divided by the live births per thawed case. RESULTS: We recruited 645 women with 840 oocyte retrieval cycles for elective oocyte freezing from November 2002 to December 2020. The overall usage rate was 8.4% (54/645). After the storage duration exceeded ten years, the probabilities of thawing oocytes were 10.6%, 26.6%, and 12.7% from women who cryopreserved their oocytes at the age ≤ 35 years, 36-39 years, and ≥ 40 years, respectively (P = 0.304). Among women who thawed their oocytes, 31.5% (17/54) of women achieved at least one live birth. For the age groups of ≤ 35 years, 36-39 years, and ≥ 40 years, the cumulative live birth rates per thawed case were 63.6%, 42.3%, and 17.6%, respectively (P = 0.045), and the cumulative costs for one live birth were $11,704, $17,189, and $35,642, respectively (P < 0.001). CONCLUSIONS: The overall usage rate was 8.4% in our cohort. The cumulative live birth rate was greatest in the youngest group and the cumulative cost per live birth was highest in the oldest group, which was threefold greater than that in the group aged ≤ 35 years. The findings added to the limited evidence of the usage rate in real-world situations, which could hopefully aid future analysis and decision-making in public health policy and for women willing to preserve fertility. TRIAL REGISTRATION: None.

Concurrent exome-targeted next-generation sequencing and single nucleotide polymorphism array to identify the causative genetic aberrations of isolated Mayer-Rokitansky-Küster-Hauser syndrome.

STUDY QUESTION: Can the use of whole-exome sequencing (WES) together with single nucleotide polymorphism (SNP) array help to identify novel causative genes of isolated Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome? SUMMARY ANSWER: OR4M2 (olfactory receptor, family 4, subfamily M, member 2) and PDE11A (phosphodiesterase 11A) gene loss-of-function variants as well as deletions at 15q11.2, 19q13.31, 1p36.21, and 1q44 were identified as possible commonly altered regions in patients with type 1 MRKH. WHAT IS KNOWN ALREADY: The isolated form of Müllerian aplasia is the most common subtype of MRKH syndrome, which invariably leads to difficulties producing offspring in affected women. However, there is little information currently available to allow for genetic testing and counseling to be performed for those affected by this syndrome. STUDY DESIGN, SIZE AND DURATION: This was a case-series genetic study. A total of seven consecutive unrelated women with type 1 MRKH were enrolled. The enrollment and experimental procedures were performed over a 2-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Whole exome-targeted next-generation sequencing and SNP array (Affymetrix Genome-Wide Human SNP Array 6.0) were performed on the first five unrelated women with type 1 MRKH syndrome. The data were combined, and the '3-hit principal' was applied on a genome-wide scale to search for the common causative genes. Quantitative PCR (qPCR) and Sanger sequencing were used to validate the identified genomic copy number losses and variants. Replication tests using direct Sanger sequencing and qPCR were performed on the remaining two women with type 1 MRKH syndrome to support the credibility of the potential candidate genes and deletions. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3443 damaging variants based on WES were shown to intersect with 1336 copy number variations (deletions) derived from the SNP array. Four highly recurrent deletions at 15q11.2 (80%), 19q13.31 (40%), 1p36.21 (40%) and 1q44 (40%) were identified in the first five women with type 1 MRKH syndrome and were considered to be novel candidate aberrations. A previously reported 1q21.1 deletion was also recurrent in two of the first five women with type 1 MRKH syndrome. The 1q44 and 19q13.31 deletions were present in at least one of the two additional patients. Damaging variants were detected in HNRNPCL1 (heterogeneous nuclear ribonucleoprotein C-like 1), OR2T2 (olfactory receptor, family 2, subfamily T, member 2), OR4M2, ZNF816 (zinc finger protein 816), and PDE11A in several of the initial five patients. Among these, the damaging variants of OR4M2 (located at 15q11.2) and PDE11A were found in at least one of the two additional patients with type 1 MRKH. LIMITATIONS, REASONS FOR CAUTION: In this study, we only searched for the deletions or damaging variants causing loss-of-function of genes in at least three of the initial five patients (3-hit criteria). Therefore, the study was designed to only detect common causative genes. Genomic duplications and/or rare individual mutations that may have also contributed to MRKH syndrome were not investigated. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated the feasibility of the use of combined data from both WES and SNP arrays for the identification of possible common causative genetic aberrations in patients with type 1 MRKH syndrome on a genome-wide scale. Further validation of our found causative genes is required before applying on genetic testing and counseling. STUDY FUNDING/COMPETING INTERESTS: The study was supported by grants from the National Science Council of Taiwan (NSC98-2314-B002-105-MY3 and NSC 100-2314-B002-027-MY3). The funding sources had no involvement in the design or analysis of the study. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.