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Individualization of stimulation protocols in IVF -- Part I

At InVia Fertility Specialists, our goal is to optimize stimulation protocols in such a way as to maximize success rates. This is to be accomplished in a manner that eliminates cycle cancellation and avoids complications such as ovarian hyperstimulation syndrome (OHSS). For many years, we have known that every patient is different and it does not make sense to use one “standard” stimulation protocol for everyone. In this blog, I would like to summarize the clinical parameters and ovarian reserve markers used by us to individualize our IVF stimulation protocols.

Background

Research studies have shown that approximately 40% of patients will abandon IVF after a single cycle. The most common cause is the physical and psychological burden of the treatment and accounted for 35% of dropout. Another common cause for the dropout was an inadequate response to ovarian stimulation, which was unexpected in most cases, with 10% of couples quitting the IVF program simply because of an inadequate response in the first cycle. It therefore makes sense for us to try and optimize the stimulation protocol the first time around and this is how we do it at InVia.

Ovarian Reserve Markers

Antral follicle count (AFC)

Antral follicle count (AFC) is the number of antral follicles (2 – 5 mm in diameter) present in the ovaries and detectable by transvaginal ultrasound scanning. These are the small follicles that will respond to gonadotropins and form large follicles (that contain the microscopic eggs). The higher the AFC, the more the number of eggs that will be retrieved.

Anti-mullerian hormone (AMH) level

Anti-mullerian hormone (AMH) level is now commonly used to assess the number of eggs (oocyte pool) that remain in the ovaries. The higher the AMH level, the larger the oocyte pool. There isn’t a definite value identified in the literature that will by itself predict ovarian response. Using the old DSL assay, the cut off was 0.7 ng /ml (5 pmol/l). With the new Gen II AMH assay the cut off value is about 40% higher and closer to 1 ng/mL.

Day-3 Follicle stimulating hormone (FSH) level

Day-3 Follicle stimulating hormone (FSH) level is a better predictor of pregnancy. Ovarian response cannot be predicted based on day-3 FSH levels. However, if there is diminished ovarian reserve (day-3 FSH level > 10 mIu/mL), one can expect poor ovarian response to stimulation.

Other factors that impact ovarian response

Previous stimulation response

It is very helpful to be able to review (if available) a previous stimulation. Based on the ovarian response and number of eggs retrieved, we can increase or decrease the dose of medications used.

Menstrual cycle characteristics

Patients with irregular cycles will often benefit from starting birth control pills so that we can then better time start of stimulation. Irregular or absent menses can be associated with polycystic ovarian disease. Concurrent hot flashes or vaginal dryness can be suggestive of ovarian failure.

 

Features suggestive of polycystic ovary syndrome (PCOS)

These include once again irregular or absent menses, increased hair (hirsutism), signs of androgen (male hormone) excess like acne, temporal balding etc. Obesity is not a diagnostic feature of PCOS. PCOS patients can be a challenge clinically. They often have high AMH levels and are high responders. At the same time, if they are obese, they may require high doses of gonadotropins for a satisfactory ovarian response.

Age

Age is an independent variable that must be considered when assessing ovarian reserve. Older women generally require a higher dose of medications to respond. There, however, are exceptions to this rule such as patients with PCOS.

Body mass index (BMI)

Obese patients will often require a higher dose of gonadotropins for a satisfactory response. It is well-established in the literature that IVF success rates are lower in obese patients. In fact when the BMI is > 35, IVF pregnancy rates are 67% lower! Currently, at InVia, we will have patients with high BMI lose weight till it is < 35 before they are accepted in our IVF program.

Smoking

Smokers will require a higher dose of medications than their non-smoking counterparts. We will not accept smokers as anonymous egg donors at InVia.

Based on a combination of the above factors, we can divide patients into 3 groups – poor responders, normal responders and high responders. Details of this and how to individualize stimulation protocols accordingly will be discussed in my next blog.

Infertility treatment IVF InVia Fertility Specialists Ovulation Induction

Dr. Vishvanath Karande

Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.

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