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Transvaginal ultrasound-guided oocyte retrieval (TVOR) is the standard method for follicular aspiration in assisted reproductive technology (ART). Although it is generally considered safe, it remains an invasive transvaginal needle procedure and may be complicated by pelvic bleeding. Large retrospective series have shown that severe complications after TVOR are uncommon in routine IVF practice1,2. Despite the overall low complication rate, clinically significant hemorrhagic events after TVOR have been well documented. Severe hemoperitoneum caused by ovarian bleeding is rare but potentially life-threatening, and cases requiring surgical management have been summarized in systematic review-level evidence3. Procedure-related bleeding has also been reported in women with underlying hemostatic abnormalities, including factor XI deficiency, von Willebrand disease, and thrombocythemia4,5,6. Additional retrospective series in donor cycles and general IVF populations have likewise supported a low overall complication rate while confirming that complications do occur7,8.
Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by structurally abnormal fibrinogen molecules9,10. Current diagnostic frameworks recommend a stepwise approach rather than reliance on a single laboratory result10,11. In practice, functional fibrinogen testing, fibrinogen antigen measurement, and thrombin time are central to diagnosis, while molecular testing can help confirm and characterize the underlying defect12,13. The clinical phenotype of CD is heterogeneous. Patients may be asymptomatic, or they may present with bleeding, thrombosis, or both14,15. This heterogeneity is emphasized in recent guidance, which recommends individualized assessment based on phenotype, laboratory pattern, and clinical context rather than laboratory abnormalities alone16. This issue is particularly relevant in ART. The peri-procedural concern is not limited to bleeding, because ART itself is associated with thromboembolic risk. In a recent systematic review and meta-analysis, the overall frequency of venous thromboembolism (VTE) associated with ART was 0.23%, and women undergoing ART had an approximately two- to threefold higher VTE risk than women with spontaneous pregnancy17. A cohort study similarly found a slightly higher incidence of pregnancy-related venous thrombosis after ART than after natural conception18. Earlier review-level evidence had already highlighted thromboembolic complications as a meaningful part of ART care19.
Accordingly, peri-procedural planning for TVOR in CD should not be framed solely as a question of whether bleeding prevention is necessary. Rather, it should be approached as a problem of individualized risk stratification that integrates bleeding phenotype, thrombotic history, prior hemostatic tolerance, procedural invasiveness, and the availability of rescue therapy16,20. Reports specifically addressing TVOR in patients with CD remain very limited, and most procedural guidance still derives from case reports or extrapolation from other surgical settings21,22,23. For that reason, the present case is important less for its rarity than for its illustration of a practical decision-making framework for conservative, risk-stratified management.
Case Presentation:
A 34-year-old Asian woman from China presented in December 2024 with infertility for more than 1 year following two ectopic pregnancies. Menarche occurred at age 13, and her menstrual cycles were regular (29–33 days). She was 153 cm tall and weighed 45 kg (body mass index, 19.22 kg/m2). Gynecologic examination was unremarkable. Her father reportedly died of cerebral hemorrhage; however, no medical records or diagnostic details were available, and this history was considered nonspecific rather than diagnostically confirmatory for an inherited bleeding disorder.
The patient had previously undergone laparoscopic left salpingotomy for ampullary ectopic pregnancy in September 2019 and January 2023. In those procedures, the estimated pelvic hematocele was approximately 100 mL and 50 mL, respectively, and intraoperative blood loss was approximately 5 mL and 10 mL, respectively. No transfusion or fibrinogen supplementation was administered perioperatively, and no abnormal bleeding was reported. Because these prior procedures were tolerated without unusual hemorrhagic complications, this surgical history was considered an important part of subsequent peri-procedural bleeding risk assessment.
Baseline laboratory testing demonstrated markedly prolonged thrombin time (TT, 33.3 s) and low functional fibrinogen (0.54 g/L). Complete blood count was within normal ranges, including hemoglobin of 132 g/L and platelet count of 208 × 109/L. These findings were relevant to peri-procedural planning because they suggested a persistent coagulation abnormality in the absence of anemia or thrombocytopenia.
Baseline reproductive evaluation supported a tubal-factor indication for in vitro fertilization. Basal reproductive hormones were not remarkable, and anti-Müllerian hormone was 0.99 ng/mL. Transvaginal ultrasound showed a normal uterus with an 8.8 mm endometrium and bilateral ovaries with 9 antral follicles each. A right hydrosalpinx (18 × 12 mm) was also identified, which was considered part of the patient’s tubal-factor infertility rather than an incidental finding and supported the decision to proceed with IVF. The male partner’s semen analysis was within normal ranges (concentration, 158.9 × 106/mL; progressive motility, 52.7%; morphology, 6%; DNA fragmentation index, 10.7%), further supporting a predominantly female tubal-factor cause of infertility.
Diagnosis, Assessment, and Plan:
Given the persistent abnormal coagulation profile, targeted next-generation sequencing of coagulation-related genes was performed, and a heterozygous FGG variant (NM_021870.3:c.902G>A, p.Arg301His) was identified, considered potentially contributory to the patient’s laboratory phenotype. Familial segregation analysis was not feasible because the patient’s father was deceased, and no additional informative family testing was available. The Sanger sequencing chromatogram is shown in Figure 1. The genetic finding strengthened diagnostic confidence and informed counseling but did not by itself determine the decision to avoid routine prophylactic transfusion, which remained based primarily on clinical phenotype, prior surgical tolerance, and peri-procedural risk assessment. Additional coagulation assessment included fibrinogen activity measured by the Clauss method, fibrinogen antigen quantitation, and the fibrinogen activity/antigen ratio, which further supported the diagnosis of a qualitative fibrinogen disorder.
The patient was diagnosed with tubal-factor infertility and congenital dysfibrinogenemia with an asymptomatic phenotype. Before treatment, a multidisciplinary team (MDT) comprising reproductive medicine, anesthesia, laboratory medicine, transfusion medicine, and internal medicine performed a structured peri-procedural risk assessment addressing both bleeding and thrombotic risks.
Several factors supported the selection of a conservative, trigger-based management strategy rather than routine prophylactic fibrinogen replacement before transvaginal oocyte retrieval. First, the patient had no personal history of spontaneous bleeding, procedure-related hemorrhage, or thrombosis, supporting a clinically mild phenotype. Second, she had previously tolerated two laparoscopic salpingotomy procedures without transfusion, fibrinogen supplementation, or abnormal perioperative bleeding, which provided reassuring real-world evidence of procedural hemostatic tolerance. Third, although functional fibrinogen was persistently low and thrombin time was prolonged, hemoglobin and platelet counts were stable, and there was no evidence of active bleeding or consumptive coagulopathy. Fourth, immediate access to rescue therapy was available, including fibrinogen-containing blood products and cross-matched red blood cells, allowing rapid escalation if clinically significant bleeding occurred. Fifth, the retrieval was planned to be performed by an experienced operator with an emphasis on minimizing puncture attempts and avoiding unnecessary procedural trauma.
The MDT also considered the competing risk that empiric prophylactic replacement might expose the patient to unnecessary treatment in the absence of a bleeding phenotype, while congenital dysfibrinogenemia itself may be associated with thrombotic as well as bleeding manifestations. Based on this integrated assessment, the patient was considered a carefully selected, low-risk candidate for conservative peri-procedural management under close surveillance.
After counseling, she elected to proceed with conventional IVF and embryo cryopreservation without preimplantation genetic testing. Embryo freezing was chosen to allow staged management: first, to complete oocyte retrieval under controlled monitoring; second, to defer embryo transfer until postprocedural recovery had been confirmed; and third, to separate the immediate peri-procedural hemostatic assessment from subsequent pregnancy-related management considerations.
The agreed peri-procedural plan was as follows: (i) no routine prophylactic transfusion before transvaginal oocyte retrieval; (ii) ensure immediate access to fibrinogen concentrate, cryoprecipitate and/or fresh frozen plasma, as well as cross-matched red blood cells; (iii) perform retrieval by an experienced operator while minimizing puncture attempts; and (iv) implement predefined post-procedure monitoring and escalation based on symptoms, vital signs, hemoglobin trends, coagulation results, and ultrasound findings.