Dec. 22, 2021
A 1990s method of in vitro fertilization (IVF) is resurging at Mayo Clinic for women of advanced reproductive age or with diminished ovarian reserve (DOR). The minimal stimulation method (MiST) IVF is less expensive and more palatable for patients than conventional IVF. MiST involves limited injectables, emphasizing oral medication.
"It's not new," says Samir Babayev, M.D., a reproductive endocrinologist at Mayo Clinic's campus in Rochester, Minnesota. "What made it come back, however, is a solution to a 1990s issue hampering oral medication use. The medications ruined uterine linings and led to low success rates in that decade."
Despite the negative effect on the uterine lining, MiST is popular outside the U.S. due to its lower cost.
Today, there's an answer for the uterine lining dilemma with oral IVF medication: a waiting period plus modern methods of embryo cryopreservation. Fertility specialists allow the affected lining to shed at the next menstruation while cryopreserving embryos for transfer during the following cycle when new lining develops. Dr. Babayev says modern MiST will enable patients to achieve the same goals as conventional IVF and experience its advantages.
For each treatment cycle, MiST involves:
- A saline infusion sonogram, mock embryo transfer
- Estrogen priming, stimulation
- Egg retrieval, fertilization
- Frozen embryo transfer preparation
- Frozen embryo transfer
MiST's side effects are no different from those of conventional IVF cycles and include breast tenderness, fatigue and food cravings, plus injection site bruising or tenderness.
MiST IVF benefits
Dr. Babayev says MiST's primarily oral treatment helps patients achieve the same goals as conventional IVF: stimulating multiple egg development. MiST's advantages include the following:
MiST uses mostly oral medication, making it less invasive and more tolerable for most patients.
Reduced medication amount
Patients receive less medication with MiST, likely decreasing side effects.
Conventional IVF uses high levels of estradiol, which increases risk of ovarian hyperstimulation syndrome (OHSS). OHSS occurs in 1 in 20 patients and ranges from mild cases to rare severe cases involving hospital admission, limb loss or death. Minimal stimulation limits OHSS risk.
The cost of MiST is lower than conventional IVF, allowing patients to repeat the treatment until successful. Dr. Babayev says decreased cost can mean the difference between conceiving a baby or not. "The health economics of MiST IVF are excellent," he says. "Because it's less expensive, it permits more treatment, especially for patients with DOR."
According to Forbes Health, facilities quote $12,000 to $14,000 a cycle on average to patients seeking IVF, though add-on charges can increase the total bill for one cycle to $15,000 to $30,000 or greater. With IVF insurance coverage still a rarity, lowering out-of-pocket costs is key to improving access for patients, Dr. Babayev says.
A 2014 publication by Dr. Frydman and colleagues in Fertility and Sterility calls lowering IVF costs a moral imperative: "We also have a fundamental obligation to increase the accessibility of IVF treatment by making it more affordable: reducing the cost of treatment by eliminating unnecessary interventions and decreasing the use of drugs."
MiST IVF drawbacks
MiST's disadvantages can include effects on the uterine lining, time frame and embryo preservation status.
Effects on the uterine lining
As previously mentioned, oral medications to stimulate egg production make the uterus uninhabitable for developing embryos for cryopreservation with frozen embryo transfer later.
MiST involves waiting for frozen embryo transfer until the next menstrual cycle when a new lining forms, prolonging the process.
Embryo preservation status
With conventional IVF, reproductive endocrinologists transfer fresh embryos. No cryopreservation occurs. Though many patients opt for fresh transfer, Dr. Babayev states that outcomes using fresh embryos are equal or inferior to those using cryopreserved embryos.
Considerations for referring patients for IVF
Dr. Babayev notes several factors that affect IVF success: age, body mass index and tobacco use.
The patient's age is the most important IVF factor. Highest success rates occur before age 40; 80% of women's eggs are chromosomally abnormal by age 40. Mayo Clinic will treat women up to age 45 using the patient's own eggs or 50 with a donor.
Body mass index (BMI)
High BMI is the second most common issue for women seeking IVF. Obesity leads to increased intubation risk, airway issues and apnea. It's harder to retrieve eggs from individuals with high BMI; pregnancy loss risk also is higher. Mayo Clinic will perform IVF for patients with BMIs lower than 42 kg/m2.
Tobacco use significantly decreases ovarian reserve and hurts reproductive outcomes.
Though age is an unmodifiable factor, Dr. Babayev says patients can change BMI and tobacco use. He also urges referring care providers to prepare patients for the fact that IVF can be challenging on the body as well as a significant medical, financial, emotional and time investment.
Mayo Clinic's IVF practice differentiators
Mayo Clinic's IVF practice is unique because patients frequently seek the program due to unsuccessful IVF at another institution. Mayo Clinic will accept patients other centers decline, such as those with higher BMI and other comorbidities.
"We offer them a second chance when they've had failed IVF treatment elsewhere," says Dr. Babayev. "We perform retrieval of even one egg for patients with low egg reserve."
Mayo Clinic's approach is more customized to each patient, as Dr. Babayev and colleagues recommend in a 2015 issue of Seminars in Reproductive Medicine. He calls Mayo Clinic's IVF program full breadth, evidence based and compassionate. "We're not a cookie-cutter clinic," he says. "We treat patients with comorbidities and undertake cases other centers won't."
For more information
Conrad, M. How much does IVF cost? Forbes Health. 2021.
Frydman R, et al. Mild approaches in assisted reproduction — Better for the future? 2014;6:1540.
Reed BG, et al. Shifting paradigms in diminishing ovarian reserve and advanced reproductive age in assisted reproduction: Customization instead of conformity. Seminars in Reproductive Medicine. 2015;33:169.