December 2024

Recent Research Publications- December 2024

Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).

Auranen A, Powell MA, Sukhin V, Landrum LM, Ronzino G, Buscema J, Bauerschlag D, Lalisang R, Bender D, Gilbert L, Armstrong A, Safra T, Nevadunsky N, Sebastianelli A, Slomovitz B, Ring K, Coleman R, Podzielinski I, Stuckey A, Teneriello M, Gill S, Pothuri B, Willmott L, Sharma S, Dabrowski C, Antony G, Stevens S, Mirza MR, Fleming E.

Ther Adv Med Oncol. 2024 Sep 28;16:17588359241277656. doi: 10.1177/17588359241277656. PMID: 39346117; PMCID: PMC11439170.

  • In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

Objectives: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

  • RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.

Methods: Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.

Results: The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.

Conclusion: The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.

Trial registration: NCT03981796.

For a full text of the article, click here: https://journals.sagepub.com/doi/10.1177/17588359241277656


Opportunities to optimize patient experience in the in vitro fertilization (IVF) clinic and the role of genetic counselors.

Chanouha N, Thoeny R, Summers K, Zorn A, Duran H, Schaa K.

J Assist Reprod Genet. 2024 Nov 15. doi: 10.1007/s10815-024-03313-4. Epub ahead of print. PMID: 39543059.

  • To understand factors influencing patient satisfaction with genetics education and psychosocial support in an IVF clinic without a genetic counselor (GC), and how the role of a GC may fill gaps in care using a mixed-method cross-sectional study.
  • Previous IVF patients (n = 133) completed a survey assessing satisfaction with genetics education and psychosocial support and decisional conflict about genetic testing. Kruskal-Wallis tests were used to compare satisfaction level to demographic and clinical variables. Spearman's correlation was used to analyze decisional conflict. Focus groups with 12 total participants expanded on themes identified in survey responses. Thematic analysis was performed using interpretive description.

Results: Participants reported satisfaction with their genetics education experience (78.9% somewhat or extremely satisfied). Satisfaction with genetics education was associated with satisfaction with information received about genetic testing results (H = 21.3, p < 0.01) and confidence using results in future decisions (H = 9.9, p < 0.01). Participants desired thorough pre-test and post-test counseling regarding genetic testing and directive guidance. Decision conflict about genetic testing was low (mean of 22.3, range 0-100). Satisfaction with genetics education was inversely correlated with decisional conflict (rs = - 0.42, p < 0.05). In-person GC visit scored highest among proposed education methods (mean score of 84.1).

  • Patients felt satisfied with genetics education and psychosocial support provided by clinical providers. Gaps in care included misconceptions regarding genetic testing, a desire for more thorough counseling about genetic testing options, more directive guidance, and increased psychosocial support through external sources such as support groups.

For a full text of the article, click here: https://link.springer.com/article/10.1007/s10815-024-03313-4


Depression in the time of COVID-19: Examination of prenatal and postpartum depression, rurality, and the impact of COVID-19.

Blocklinger KL, Gumusoglu SB, Kenney AS, Faudel AJ, Faro E, Brandt DS, Knosp B, Davis HA, Hunter SK, Santillan MK, Santillan DA.

J Affect Disord. 2024 Oct 28;370:337-347. doi: 10.1016/j.jad.2024.10.081. Epub ahead of print. PMID: 39490676.

  • To determine the impact of the COVID-19 pandemic on prenatal and postpartum depressive symptoms in rural versus urban populations.
  • A retrospective cohort study was conducted among 24,227 cisgender women who gave birth from 2010 to 2021 at an academic medical center located in a rural midwestern state. Exclusion criteria were <18 years old, incarcerated, or without a documented zip code. The Patient Health Questionnaire-9 (PHQ-9) was administered during pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) during postpartum. A sub-cohort also completed a COVID-related questionnaire. Rurality was defined as living in a county with <50,000 people. The COVID-19 era was defined as 1/1/2020 to 9/25/2021. Chi-square and Fisher exact tests were used as appropriate. Significance was set at α < 0.05.

Results: Rural participants were more likely (p ≤ 0.001) to exhibit clinical depression symptoms before the pandemic in both the prenatal (8.63 % of rural participants vs. 6.49 % of urban participants) and postpartum periods (11.19 % rural vs. 9.28 % urban). During the pandemic, urban participants had increased postpartum depression. Rural participants endorsed more financial and labor concerns, whereas urban participants expressed support system concerns.

Limitations: Study data were gathered from participants who gave birth at a single, midwestern hospital. Results may not be widely generalizable given the homogeneity of participants.

Conclusions: Rural women experienced higher rates of prenatal and postpartum depressive symptoms compared to their urban counterparts. The COVID-19 pandemic was a significant stressor, revealing specific mental health vulnerabilities among birthing people.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0165032724017762?via%3Dihub


Pembrolizumab-induced cytokine release syndrome with severe encephalopathy in the setting of clear cell vaginal carcinoma: A case report.

Metzger S, Ulmer K, Hill EK.

Gynecol Oncol Rep. 2024 Oct 11;56:101529. doi: 10.1016/j.gore.2024.101529. PMID: 39494393; PMCID: PMC11530849.

•Pembrolizumab is increasingly used in the treatment of gynecologic cancers and has a half-life of 26 days.

  • Cytokine release syndrome with severe encephalopathy is a rare immune-mediated adverse effect.

•Supportive care remains an important part of treatment of immune-mediated toxicity. It takes 5 half-lives to clear Pembrolizumab from the body.

For a full text of the article, click here: https://pmc.ncbi.nlm.nih.gov/articles/PMC11530849/


Should We Rescue Clubbed Fallopian Tubes?

Kroeger MG, Kresowik JD.

Fertil Steril. 2024 Oct 30:S0015-0282(24)02341-0. doi: 10.1016/j.fertnstert.2024.10.039. Epub ahead of print. PMID: 39486502.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224023410?via%3Dihub


Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

Lee JM, Brady MF, Miller A, Moore RG, MacKay H, McNally L, Lea J, Street D, Lheureux S, McDonald ME, Duska LR, Cantuaria G, Kavecansky J, Leath CA 3rd, Powell M, Cadungog MG, Rose PG, Kim YM, Huang HQ, Provencher M, Wenzel LB, Bookman MA, Kohn EC, Secord AA

J Clin Oncol. 2024 Oct 3:JCO2400683. doi: 10.1200/JCO.24.00683. Epub ahead of print. PMID: 39361946.

  • We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC).

Patients and methods: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes.

  • Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725).

Conclusion: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

For a full text of the article, click here: https://ascopubs.org/doi/pdf/10.1200%2FJCO.24.00683


Regulator of G-Protein Signaling 2 Knockout in CD4+ T Cells Promotes Anti-Inflammatory T Cells, Enhancing Ovulation, and Oocyte Yield.

Raff M, Benton T, Brummond D, Kovach D, Bunton O, Janky E, Duran EH, Scroggins DG, Gray G, Scroggins SM.

bioRxiv [Preprint]. 2024 Oct 18:2024.10.15.618561. doi: 10.1101/2024.10.15.618561. PMID: 39464145; PMCID: PMC11507868.

Objective: To determine the downstream effects on ovarian function and immune cell differentiation in the ovary and uterus using a model in which RGS2 was knocked out specifically in CD4+ T cells.

Design: Laboratory based experiments with female mice.

  • Female congenic (fully backcrossed) and non-congenic (mixed strain) mice with CD4 T cell-specific RGS2 knockout.
  • Four-week-old female CD4 RGS2 knockout (CD4 RGS2 KO ) mice and their littermate controls (CD4 RGS2 CTL ) were subjected to superovulation using pregnant mare serum gonadotropins.

Main outcome measures: Oocyte numbers, lymphocyte populations in the ovary and uterus, and serum estradiol and progesterone concentrations.

  • In non-congenic (mixed strain) mice, CD4 RGS2 knockout (KO) promoted higher oocyte ovulation and increased uterine total leukocyte numbers. Similarly, congenic (fully backcrossed strain) mice showed higher oocyte numbers and increased uterine total leukocytes in the CD4 RGS2 KO mice compared to CD4 RGS2 CTL mice. Pro-inflammatory CD4+ T helper (T H ) 1 and T H 17 cell frequencies in the ovary and uterus were unchanged, while Treg and T H 2 cell frequencies were elevated, along with increased concentrations of estradiol and progesterone in the serum of CD4 RGS2 KO mice.

Conclusion: Our study highlights the important role of RGS2 in CD4+ T cells within the context of reproduction. The dysregulation of immune responses due to RGS2 knockout in CD4+ T cells appears to enhance oocyte production. Further research is warranted to elucidate the precise mechanisms by which RGS2 influences reproductive outcomes, including its impact on fecundability, endometrial receptivity, and successful implantation.

For a full text of the article, click here: https://www.biorxiv.org/content/10.1101/2024.10.15.618561v1


Load-dependent mechanisms contribute to increased aortic stiffness among women with a history of preeclampsia: relation with cardiovagal baroreflex sensitivity.

Davis KG, Armstrong MK, Nuckols VR, Smith MN, Pewowaruk R, Gimblet CJ, Santillan DA, Santillan MK, Pierce GL.

Am J Physiol Heart Circ Physiol. 2024 Dec 1;327(6):H1406-H1412. doi: 10.1152/ajpheart.00556.2024. Epub 2024 Oct 18. PMID: 39423036.

Preeclampsia, a hypertensive disorder of pregnancy, results in increased lifetime cardiovascular disease (CVD) risk. Total aortic stiffness, a robust risk factor for CVD, is composed of load-dependent (blood pressure load on arterial wall) and structural (intrinsic changes in arterial wall) mechanisms. Total aortic stiffness is also associated with reduced cardiovagal baroreflex sensitivity (BRS). We sought to determine 1) whether elevated total aortic stiffness among women with a history of preeclampsia (hxPE) is attributed to load-dependent or structural stiffness, and 2) whether either mechanism is associated with lower BRS. Total aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal BRS (sequence technique) were measured among women 1-5 yr postpartum (n = 115; age 34 ± 4 yr; hxPE n = 51; controls n = 64). Structural aortic stiffness was calculated from participant-specific exponential models by standardizing aortic stiffness to a "reference" blood pressure. Load-dependent stiffness was calculated as total minus structural stiffness. Total [+0.8 m/s, 95% confidence interval (CI) (-0.99, -0.23), P = 0.002] and load-dependent [+0.4 m/s, 95% CI (-0.56, -0.22), P < 0.001], but not structural [95% CI (-0.52, 0.08), P = 0.16] aortic stiffness were higher among women with a hxPE compared with controls. Women with a hxPE had lower BRS (P = 0.042) that was negatively associated with total [B = -3.24 ms/mmHg, 95% CI (-6.35, -0.13), P = 0.042] and load-dependent [B = -5.91 ms/mmHg, 95% CI (-11.31, -0.51), P = 0.033] aortic stiffness. Load-dependent, not structural, aortic stiffness mechanisms contribute to higher total aortic stiffness among women with a hxPE and are associated with lower cardiovagal BRS. Postpartum monitoring for high BP is critical to reduce increased CVD risk after preeclampsia.NEW & NOTEWORTHY The novel finding is that load-dependent stiffness, not structural stiffness, is the primary mechanism of aortic stiffness, and is associated with reduced baroreflex sensitivity in women with a history of preeclampsia. These findings may help tailor high blood pressure prevention and management strategies in this population to prevent structural aortic stiffening, altered baroreflex control, and increased lifetime cardiovascular disease (CVD) risk.

For a full text of the article, click here: https://journals.physiology.org/doi/full/10.1152/ajpheart.00556.2024


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Fertil Steril. 2024 Oct 8:S0015-0282(24)02004-1. doi: 10.1016/j.fertnstert.2024.08.351. Epub ahead of print. PMID: 39387775.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224020041?via%3Dihub


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Am J Obstet Gynecol MFM. 2024 Oct 7:101481. doi: 10.1016/j.ajogmf.2024.101481. Epub ahead of print. PMID: 39393968.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2589933324002076?via%3Dihub


Trustworthiness Criteria for Meta-Analyses of Randomized Controlled Studies: OBGYN Journal Guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Gynecol Obstet Invest. 2024 Oct 3:1-5. doi: 10.1159/000541479. Epub ahead of print. PMID: 39362189.

For a full text of the article, click here: https://karger.com/goi/article/doi/10.1159/000541479/914242/Trustworthiness-Criteria-for-Meta-Analyses-of


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

BJOG. 2024 Oct 2. doi: 10.1111/1471-0528.17945. Epub ahead of print. PMID: 39356178.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17945


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Ultrasound Obstet Gynecol. 2024 Oct 2. doi: 10.1002/uog.29118. Epub ahead of print. PMID: 39356156.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.29118


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN Journal guidelines.

OBGYN Editors’ Integrity Group (OGEIG). Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Int J Gynaecol Obstet. 2024 Nov;167(2):475-478. doi: 10.1002/ijgo.15885. Epub 2024 Oct 2. PMID: 39356118.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.15885


Trustworthiness criteria for meta-analyses of randomized controlled studies: OBGYN Journal guidelines.

OBGYN Editors' Integrity Group (OGEIG); Berghella V.  Catherine S. Bradley (Am J Obstet Gynecol) and Donna Santillan (Proceedings Obstet Gynecol), are members of OGEIG

Acta Obstet Gynecol Scand. 2024 Nov;103(11):2118-2121. doi: 10.1111/aogs.14942. Epub 2024 Sep 22. PMID: 39306746; PMCID: PMC11502421.

For a full text of the article, click here: https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.14942


ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic.

Streeter J, Persaud L, Gao J, Manika D, Fairman W, García-Peña LM, Marti A, Manika C, Gaddi S, Schickling B, Pereira RO, Abel ED.

Front Endocrinol (Lausanne). 2024 Sep 24;15:1325286. doi: 10.3389/fendo.2024.1325286. PMID: 39381436; PMCID: PMC11458430.

Introduction: Reducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model.

  • We generated mice with homozygous floxed Opa1 and Atf4 alleles and a tamoxifen-inducible Cre transgene controlled by the human skeletal actin promoter to enable simultaneous depletion of OPA1 and ATF4 in skeletal muscle (mAO DKO). Mice were fed high fat (HFD) or control diet and evaluated for ISR activation, body mass, fat mass, glucose tolerance, insulin tolerance and circulating concentrations of FGF21 and growth differentiation factor 15 (GDF15).
  • In mAO DKO mice, ATF4 induction is absent. Other indices of ISR activation, including XBP1s, ATF6, and CHOP were induced in mAO DKO males, but not in mOPA1 or mAO DKO females. Resistance to diet-induced obesity was not reversed in mAO DKO mice of both sexes. Circulating FGF21 and GDF15 illustrated sexually dimorphic patterns. Loss of OPA1 in skeletal muscle increases circulating FGF21 in mOPA1 males, but not in mOPA1 females. Additional loss of ATF4 decreased circulating FGF21 in mAO DKO male mice, but increased circulating FGF21 in female mAO DKO mice. Conversely, circulating GDF15 was increased in mAO DKO males and mOPA1 females, but not in mAO DKO females.
  • Sex differences exist in the transcriptional outputs of the ISR following OPA deletion in skeletal muscle. Deletion of ATF4 in male and female OPA1 KO mice does not reverse the resistance to DIO. Induction of circulating FGF21 is ATF4 dependent in males, whereas induction of circulating GDF15 is ATF4 dependent in females. Elevated GDF15 in males and FGF21 in females could reflect activation by other transcriptional outputs of the ISR, that maintain mitokine-dependent metabolic protection in an ATF4-independent manner.

For a full text of the article, click here: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1325286/full


AptamerRunner: An accessible aptamer structure prediction and clustering algorithm for visualization of selected aptamers.

Ruiz-Ciancio D, Veeramani S, Singh R, Embree E, Ortman C, Thiel KW, Thiel WH.

Mol Ther Nucleic Acids. 2024 Oct 9;35(4):102358. doi: 10.1016/j.omtn.2024.102358. PMID: 39507401; PMCID: PMC11539416.

Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for targets and are generated using the iterative systematic evolution of ligands by exponential enrichment (SELEX) process. Next-generation sequencing (NGS) revolutionized aptamer selections by allowing a more comprehensive analysis of SELEX-enriched aptamers as compared to Sanger sequencing. The current challenge with aptamer NGS datasets is identifying a diverse cohort of candidate aptamers with the highest likelihood of successful experimental validation. Here we present AptamerRunner, an aptamer sequence and/or structure clustering algorithm that synergistically integrates computational analysis with visualization and expertise-directed decision making. The visual integration of networked aptamers with ranking data, such as fold enrichment or scoring algorithm results, represents a significant advancement over existing clustering tools by providing a natural context to depict groups of aptamers from which ranked or scored candidates can be chosen for experimental validation. The inherent flexibility, user-friendly design, and prospects for future enhancements with AptamerRunner have broad-reaching implications for aptamer researchers across a wide range of disciplines.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2162253124002452?via%3Dihub


Initially categorized 46,XY embryo transfer ending with 45,X products of conception-a case report and a review of discordant result management.

Singh P, Snider A, Kayali R, Mancuso A.

F S Rep. 2024 May 22;5(3):328-332. doi: 10.1016/j.xfre.2024.05.006. PMID: 39381658; PMCID: PMC11456636.

  • : To report a case of an initially categorized euploid male embryo screened using preimplantation genetic testing (PGT) resulting in miscarriage and testing of products of conception consistent with Turner syndrome, and to discuss additional workup and considerations in cases of discrepancy.
  • : Case report.

Setting: University fertility clinic.

  • Frozen single embryo transfer of a euploid male embryo.
  • A couple seeking procreative management for a female partner having a balanced translocation 46,XX,t(14;16)(q21;q21) diagnosed after the couple's previous child passed because of segmental duplication in chromosomes 14 and 16 and pursued in vitro fertilization treatment for PGT for structural rearrangements.

Main outcome measures: Miscarriage with discordant chromosomal microarray result.

  • Couple conceived with the transfer of a euploid male embryo. After the initial confirmation of pregnancy, repeat imaging indicated a missed abortion. Dilation and curettage were performed, and the products of conception were sent for chromosomal microarray. Results indicated Turner syndrome (45,X). Follow-up short tandem repeat analysis confirmed the products of conception were from the tested embryo. After reevaluation of the data, copy number variations below the reporting threshold for the sex chromosomes were observable and compatible with mosaic 45,X/46,XY.
  • The limitations of PGT should be kept in mind when counseling patients because of both the sample provided by biopsy, the sequencing platforms and the laboratory pipeline for diagnosis. We recommend that patients be counseled about these limitations and offered antenatal and postnatal testing as indicated. When discrepancies are seen after PGT, collaboration with the reference laboratory and additional testing with short tandem repeat analysis should be considered when possible.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2666334124000576?via%3Dihub


Intracytoplasmic sperm injection versus conventional in vitro fertilization in unexplained infertility.

Iwamoto A, Summers KM, Sparks A, Mancuso AC

F S Rep. 2024 Jun 19;5(3):263-271. doi: 10.1016/j.xfre.2024.06.003. PMID: 39381653; PMCID: PMC11456666.

  • To compare cumulative live birth rate (CLBR) and cost-effectiveness of intracytoplasmic sperm injection (ICSI) vs. conventional in vitro fertilization (cIVF).

Design: Retrospective cohort study of cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System.

  • Society for Assisted Reproductive Technology (SART) member IVF clinics in the United States.
  • Patients with unexplained infertility who underwent first autologous retrieval cycles between January 2017 and December 2019 with linked fresh and frozen embryo transfers through December 2021.
  • : ICSI vs. cIVF.

Main outcome measures: The primary outcome was CLBR, defined as ≤1 live birth from a retrieval cycle and all linked embryo transfers. Secondary outcomes included two pronuclear (2PN) per oocyte retrieved, miscarriage rate, and total number of transferred or frozen embryos per 2PN. Subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A) were analyzed. Outcomes were adjusted for age, body mass index, number of oocytes retrieved, length of follow-up, and clinic ICSI use rate.

Results: A total of 18,805 patients with unexplained infertility were included. No difference in CLBR was found among cycles without genetic testing (54.4% ICSI vs. 57.5% cIVF) and with PGT-A (47.6% ICSI vs. 51.8% cIVF). Intracytoplasmic sperm injection cycles without genetic testing had a higher miscarriage rate (16.4% vs. 14.4%) but no difference was seen in cycles with PGT-A (13.9% ICSI vs. 13.2% cIVF). Intracytoplasmic sperm injection cycles had a significantly lower ratio of 2PN per oocyte retrieved without genetic testing (59.7% vs. 60.9%) and with PGT-A (63.3% vs. 65.8%). The ratio of embryos transferred or frozen per 2PN was not significantly different in cycles without genetic testing (49.4% vs. 49.6%) or with PGT-A (54.2% vs. 55.2%). Total fertilization failure occurred in 216 patients (4%) who underwent cIVF and in 153 patients (1.1%) who used ICSI.Compared with cIVF alone, an estimated additional $11,011,500 was charged to patients for ICSI without genetic testing and $9,010,500 was charged to patients for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics. On the basis of total fertilization failure rates, 35 patients would require treatment with routine ICSI to avoid a single cycle of total fertilization failure with cIVF.

  • Routine use of ICSI in unexplained infertility is not warranted due to the additional cost and lack of CLBR benefit.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S2666334124000746?via%3Dihub


To see or not to see? That is the miscarriage management question.

Salari S, Lindheim SR.

Fertil Steril. 2024 Sep 18:S0015-0282(24)02234-9. doi: 10.1016/j.fertnstert.2024.09.021. Epub ahead of print. PMID: 39299568.

For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0015028224022349?via%3Dihub