Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1 percent of the population, though clinically significant symptoms occur in about 1 in 10,000 individuals. It is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a protein critical for blood clotting. For women, VWD poses unique challenges during reproductive years, particularly in the context of fertility and assisted reproductive technologies like in vitro fertilization (IVF). This comprehensive analysis explores how VWD affects fertility, the specific risks associated with IVF, and the management strategies to ensure safe and effective treatment, drawing on current medical literature and guidelines as of June 1, 2025.

What is von Willebrand disease?

Von Willebrand disease is the most common inherited bleeding disorder, affecting up to 1 in 100 individuals in the general population—though clinically significant symptoms occur in about 1 in 10,000. It stems from a deficiency or dysfunction in von Willebrand factor (VWF), a protein essential for normal blood clotting. Women with this condition are particularly vulnerable during reproductive years, where menstruation, conception, pregnancy, and delivery all pose bleeding risks.

VWD is classified into three main types, each with varying severity and bleeding risks:

• Type 1: Partial quantitative deficiency of VWF, accounting for approximately 75 percent of cases, typically mild.
• Type 2: Qualitative dysfunction of VWF, with subtypes (2A, 2B, 2M, 2N), comprising approximately 20 percent of cases.
• Type 3: Near-complete or total deficiency of VWF, rare and severe.

These variations matter because bleeding risk during IVF depends not only on whether a patient has VWD but on the type and severity.

Women with VWD are particularly vulnerable during reproductive events such as menstruation, conception, pregnancy, and delivery, all of which can exacerbate bleeding tendencies. Despite its prevalence, VWD often goes undiagnosed, as many women normalize symptoms like heavy menstrual bleeding until a procedure, such as egg retrieval, reveals their condition.

When to suspect VWD

VWD should be considered in women presenting with:

• Heavy or prolonged menstrual bleeding (menorrhagia).
• Frequent nosebleeds or easy bruising.
• Excessive bleeding after dental procedures or minor cuts.
• A family history of bleeding disorders.
• Postpartum hemorrhage in prior pregnancies.

Unfortunately, many women normalize these symptoms until a fertility procedure—such as egg retrieval—reveals their underlying bleeding tendency.

Implications for fertility

While VWD does not directly cause infertility, it can indirectly affect fertility through several mechanisms:

• Menorrhagia and anemia: Heavy menstrual bleeding is a hallmark symptom, often leading to iron deficiency anemia, which can disrupt ovulatory function or reduce implantation rates. This can impact overall reproductive health and fertility outcomes.
• Pregnancy complications: Women with VWD have a higher risk of spontaneous abortion, particularly in early pregnancy. Studies indicate that 20–25 percent of women with VWD experience delayed postpartum hemorrhage, which is 15–20 times more common than in the general population. These complications can influence fertility planning.
• Genetic considerations: VWD is often inherited in an autosomal dominant pattern, with a 50 percent chance of transmission to offspring. Genetic counseling is recommended for women planning pregnancy to understand the risks and implications for future generations.

IVF-specific risks and considerations

IVF, involving ovarian stimulation, egg retrieval, and embryo transfer, poses specific challenges for women with VWD due to increased bleeding risks. The following details outline these risks and management strategies:

Feasibility and risks

IVF is feasible for women with VWD, but it carries heightened bleeding risks due to the invasive nature of the procedures. Key risks include:

• Hormonal stimulation: Daily subcutaneous injections can cause hematomas or prolonged bleeding at injection sites.
• Oocyte retrieval: Transvaginal aspiration under ultrasound guidance using a needle can lead to significant bleeding, particularly if VWF levels are low. A case study reported recurrent hemorrhage after oocyte retrieval in a woman with undiagnosed VWD, underscoring the need for screening.
• Ovarian hemorrhage: A rare but life-threatening complication during ovarian stimulation, requiring immediate medical attention for symptoms like sudden pelvic pain or pressure.
• Embryo transfer: Manipulation of the cervix or uterus, though minimally invasive, may lead to unexpected bleeding in patients with low clotting factors.

How to safely proceed: A multidisciplinary approach

IVF is possible for women with VWD when it is planned properly. Here’s what that looks like in practice:

Comprehensive pre-IVF workup:

• Measure VWF antigen, ristocetin cofactor activity, and factor VIII levels to assess bleeding risk.
• Determine the type and severity of VWD to tailor management.

Hematologic support:

• For Type 1 or mild cases, desmopressin (DDAVP) can be used to transiently raise VWF and factor VIII levels.
• For moderate to severe cases (Type 2/3), VWF-containing factor VIII concentrates may be necessary.
• Develop a personalized prophylaxis plan in collaboration with a hematologist.

Close procedural monitoring:

• Inform reproductive endocrinology and anesthesiology teams about the patient’s condition.
• Ensure availability of factor replacement or DDAVP on the day of egg retrieval.

Post-procedure and pregnancy surveillance:

• Monitor for delayed bleeding complications.
• During pregnancy, VWF levels naturally increase, but they drop sharply postpartum (within 14–21 days), necessitating careful planning for delivery and recovery. A retrospective study found that women with VWD were more likely to require blood transfusions after childbirth due to postpartum hemorrhage.

Bridging the gap between specialties

Reproductive endocrinologists and hematologists must collaborate closely to manage women with VWD undergoing IVF. This multidisciplinary approach ensures that bleeding risks are minimized and complications are addressed promptly. Physicians should be vigilant in screening for VWD, as symptoms like heavy menstrual bleeding are often normalized, delaying diagnosis until a procedure reveals the condition.

Guidelines and recommendations

Several authoritative guidelines provide direction for managing VWD in the context of fertility and IVF:

• NHLBI Guidelines (2008): Emphasize preconception evaluation and individualized management plans based on VWF and factor VIII levels.
• ACOG Committee Opinion (2013): Recommends screening for VWD in women with heavy menstrual bleeding and stresses collaboration with hematologists for gynecologic and obstetric care, including IVF.
• ASH ISTH NHF WFH Guidelines (2021): Focus on diagnosis and management, highlighting patient-reported outcomes and individualized care, applicable to fertility treatments.

Summary of VWD management in IVF

• IVF feasibility: IVF is possible for women with VWD, but bleeding risks are increased.
• Bleeding risks: Includes hormone injection sites, egg retrieval, and ovarian hemorrhage risk.
• Management strategies: Preprocedure VWF/factor VIII evaluation, desmopressin, factor replacement, multidisciplinary care.
• Post-IVF monitoring: Close monitoring postpartum due to return of VWF levels to baseline.

Conclusion

Von Willebrand disease poses significant challenges for fertility and IVF treatment due to increased bleeding risks, but these can be effectively managed with appropriate medical interventions and multidisciplinary care. Women with VWD should undergo thorough evaluation and planning with hematologists and reproductive specialists to ensure safe and successful fertility treatments. The current evidence, as of June 1, 2025, supports the feasibility of IVF for women with VWD, provided that proper precautions and management strategies are in place. Physicians must remain vigilant in screening for VWD and fostering collaboration between specialties to honor both the biological and aspirational needs of their patients. Continued research is needed to refine these approaches and improve outcomes for this population.

Oluyemisi (Yemi) Famuyiwa is a renowned fertility specialist and founder, Montgomery Fertility Center, committed to guiding individuals and couples on their path to parenthood with personalized care. With a background in obstetrics and gynecology from Georgetown University Hospital and reproductive endocrinology and infertility from the National Institutes of Health, she offers cutting-edge treatments like IVF and genetic testing. She can be reached on Linktr.ee, LinkedIn, YouTube, Facebook, Instagram @montgomeryfertility, and X @MontgomeryF_C.