Lesson 2 of 6
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Fertility on a Budget

Lesson 2 of 6

Which Types of Treatments & Approaches

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Adjusting Diet & Lifestyle

For many patients, making adjustments to diet, lifestyle, and exercise patterns are relatively cost efficient and in some cases, can reduce the need for costly treatment or raise the odds of success treatments work earlier on in the process.

We have a detailed, comprehensive, and rigorous course on the subject (here), but here we provide a few examples of how improvements can increase success rates and thus decrease costs.

Smoking

When a man or woman smokes it drives down the odds of conceiving naturally by 50%–60%. Thus, quitting smoking may reduce the odds costly treatment will be necessary.

Relative Odds of Natural Conception

If IVF is needed, success rates are twice as high when neither party smokes. Reducing the odds of needing an additional IVF cycle by half is meaningful.

Pregnancy Rates by Male & NonSmokers

Weight Loss Specific to PCOS Patients

Another example of how lifestyle adjustments can improve outcomes would be for women who have Polycystic Ovarian Syndrome (PCOS), have a high body mass index, and irregular cycles.

When these women adjust diet and lifestyle before advancing to treatment, the odds of success tend to skyrocket, reducing the need for more costly follow-on interventions.

Below is an example of how diet and exercise transforms the odds of success that inexpensive, oral medications will work, in turn reducing the need for costly approaches like IUI or IVF.

Success Rates after 4 clomid cycles in PCOS patients

Folate & Folic Acid

Amongst fertility patients trying to conceive with IVF, success rates closely correspond with the amount of folate consumed (through food or supplements). Folate can be found in any number of readily-accessible foods, and as you can see below, higher volumes of intake correspond with higher rates of IVF success.

IVF Success Rates and Folic Acid Intake

IUI vs IVF

Different treatments drive variable costs and may be more productive for certain patients than others. As an example, below are sample cost ranges for the most common approaches: oral medication, intrauterine insemination (IUI), and in vitro fertilization (IVF).

Comparing Fertility Treatment Cost

A major point of debate is when patients should start or stop IUI in favor of IVF. IUI tends to be far less costly than IVF, but its odds of success depend upon patient type.

Patients for Whom IUI Does or Doesn't Help

To draw out the example, see the below odds of IUI success for two vastly different patient types: single women in their 30s and women over age 42.

Thus, for some patients where IUI is appropriate, it can be productive on a cost-per-delivery basis (maybe more so than as we showcase below.)

Cost and Value of IUI vs IVF

However, for many patients, the odds IUI will work after a few cycles quickly approaches zero. You can see that in the cumulative odds of success graph below, noting that after the third or fourth cycle, the lie flattens. As a result, each successive IUI cycle becomes more costly if we calculate it on a “cost per baby basis” (cost of IUI divided by the percentage odds of a birth from that IUI).

Implied Cost for Gonadotropin IUI

We have detailed courses on both IUI (here) and IVF (here), as well as lessons with side-by-side comparisons (here), which we suggest you consult.

Evaluating Treatment Add-Ons

In addition to the baseline costs of an IVF cycle, many patients will be presented with add-ons or supplemental interventions with the hope of improving odds of success. All of these add-ons represent additional cost to the patient, however many of these add-ons are lacking reliable data regarding their efficacy and may provide little value in improving live birth rates for most patients.

The Human Fertilisation & Embryology Authority (HFEA) of the UK has developed a “traffic light” rating system, in which they evaluate the quality of the evidence available to support the effectiveness of these treatment add-ons.

A green rating indicates there has been more than one high-quality, randomized control trial (RTC) indicating that the intervention is effective at improving outcomes for most fertility patients.

An amber rating indicates there is conflicting evidence, that the evidence is not conclusive, and further research is needed.

A red rating indicates there is no evidence from RTCs showing that the intervention is effective at improving chances of a live birth for most patients.

It’s important to note that the rating is based on the evidence for improving outcomes for most patients, and does not necessarily mean that a specific intervention may not be worthwhile for some patients.

For example, genetic screening of embryos or PGT-A is given a “red” rating by the HFEA, however, some patients may find personal benefit in PGT-A, depending on their priorities in treatment. We discuss this in the chapter below, and in greater detail in the dedicated PGT-A course.

Here you can see several popular IVF add-ons as rated by the HFEA.

HFEA UK Chart

IVF Using ICSI

Should you consider IVF, there’s a 65%–95% likelihood your clinic will want to use a technique called intracytoplasmic sperm injection (ICSI) to fertilize the eggs. While the below data comes from U.S. reporting, this is a global phenomenon.

We have a dedicated course (here) on the nuances of ICSI, and we suggest you give it a close look, but for the moment, these are the salient points:

  • ICSI can often comprise 10%–25% of the total cost of an IVF cycle
  • Only for very specific cases (comprising the minority of patients) has ICSI been consistently proven to increase the odds of a live birth

Which Fertilization Approach Drives Higher Birth Rates

As with any treatment intervention, it’s important to discuss with your doctor the trade-offs, but in the case of ICSI, you may find the clinic deploys ICSI solely to provide you reassurance your “eggs will fertilize” (a necessary, but merely interim, step) though it won’t impact the odds you bring home a child (the point of treatment).

IVF Using PGT-A

If you’re considering IVF, your clinic may be interested in testing (using a diagnostic called PGT-A) your embryos to set aside those that have the wrong number of chromosomes and are far less likely to result in a healthy live birth.

As with ICSI, we have a dedicated course to PGT-A (here), and we suggest you give it a close look. The value of PGT is debated amongst credible clinicians and is often case-specific.

That said, many private clinics insist upon doing it for the majority of their patients despite two facts:

  • PGT-A can add an additional 10%–30% to the cost of an IVF cycle
  • It seldom—if ever—improves the odds the IVF cycle will lead to a baby

That said, PGT-A can play an important role in reducing IVF transfers that aren’t likely to lead to a birth, possibly culminating in miscarriage. Yet, this is not equally true for all IVF patients.

Below is data collected from 34 clinics across three continents that reflects PGT-A most meaningfully improves transfer rates in women 35 and older.

Utility of PGT-A in IVF Success Rates

As with ICSI, it’s critical to discuss with your doctor the trade-offs of any treatment choice. Specifically with PGT-A, there can be credible arguments on how using it could needlessly cost money, or save money, depending upon factors like female age, results from previous cycles, family building goals (e.g. number of children and with what spacing) and more.

Endometrial Receptivity Testing in IVF

The ERA test was developed to deduce whether the endometrium is receptive to an embryo, and to predict a woman’s personal window of implantation. Over the past few years, the ERA test has become a popular option for those seeking answers on why their embryos have failed to implant, however as you can see in the chart above, the lack of evidence that it improves outcomes has earned the ERA test a “red” rating by the HFEA.

The ERA is a molecular diagnostic test of the endometrium, obtained by biopsy.

In the United States, the biopsy itself averages $200 and the test is approximately $600-$1000. Neither is typically billed to insurance so patients will have to foot the cost themselves. Similarly, in Brazil and Japan, an ERA test will set you back around the equivalent in local currency: approximately R$5,000 and ¥118,000 respectively.

Clinical Data on ERA Effectiveness

As you can see in the chart above, the HFEA gave the ERA a "red" rating. We'll explain the data available below.

Patients Who Have Yet to Have a Failed Transfer

The first adequately powered randomized controlled trial of ERA-guided receptivity-timed transfers was published by Doyle et al. in December 2022 and has poured cold water on the notion that the ERA test is of much value in predicting the window of implantation. The study compared live births from single euploid (genetically normal, as determined by PGT-A screening) frozen embryo transfers in ERA-guided vs. standardized transfers. Participants who did not have euploid blastocysts were excluded. 767 participants were included in the study and the mean age was 35 years. The study was double-blinded meaning that neither the participants nor the investigators knew which treatment the study subjects were receiving and the participants were randomly assigned to their treatment groups.

All control group participants and those intervention group participants with receptive ERA results received frozen embryo transfer at the standard timing of 123 ± 3 hours after the start of progesterone, while the intervention group participants with nonreceptive ERA results underwent frozen embryo transfer based on the recommended timing from the endometrial receptivity results as shown in the table below.

The primary outcome was live birth. Secondary outcomes included clinical pregnancy, biochemical pregnancy, chemical pregnancy, and ongoing pregnancy. The data showed that there were no significant differences between groups for any of the outcomes. The table below shows the results of the primary outcome (live births) and one secondary outcome (clinical pregnancy) for all patients.

Further subgroup analyses showed that there were no statistically significant differences between patients who were deemed nonreceptive by ERA testing across groups as shown in the table below.

Taken together, the data from this double-blind, randomized, controlled trial show that endometrial receptivity testing provided no significant advantage in live birth rates—or any other positive clinical outcome—compared with standard timing for frozen embryo transfer with PGT-A tested euploid embryos.

Patients Who Have Experienced a Previous Failed Transfer

For patients who have had a previous embryo transfer that has failed, the data also indicate that ERA is not helpful in improving outcomes. That said, embryo transfers can fail for a variety of reasons, and despite the conclusions outlined below, proponents of ERA argue it has yet to be proven ineffective for those suffering from recurrent implantation failure (RIF), whereby on multiple occasions transfers failed because embryos did not successfully embed in the endometrium.

Patients experiencing recurrent implantation failure may benefit from considering alternative treatments, which are discussed in more detail in this lesson.

Donor Egg & Other Third Party Approaches

Laws vary region-to-region on whether hopeful parents can use donated eggs, donated sperm, or the help of a gestational surrogate.

As for using donor eggs, we have a detailed course we suggest you consult here, but to oversimplify a few facts:

  • Success rates with donor eggs are high compared to using one’s own eggs
  • IVF cycles using donated eggs tend to cost substantially more

To elucidate the first point, let’s look at U.K. data comparing IVF success rates using donor eggs versus the success rates for women using their own eggs over age 42, as an example.

In some countries, adding the cost of donor eggs to an IVF cycle can be substantial. In the U.S. context (and with many exceptions), it can be reasonable to assume an additional $15,000 of cost (with ranges from $5,000–$35,000).

Many factors play into the decision to use donor eggs, but on a purely financial basis (and depending upon the circumstances), here’s one way to look at the value.

Below we calculate the costs required to achieve even 50-50 odds of success with IVF for:

  • A female patient using donor eggs
  • A female patient using their own eggs after age 42

The increased odds of success per cycle (40% vs 2%) more than compensate for the increased cost per cycle ($35,000 - $20,000 = $15,000). Hence, the “cost to target’ (again, 50-50 odds of a live birth) are nearly 80% lower ($42,000 vs $500,000) for the patient who uses donor eggs.

We should point out that this is just an example, and for many patients (e.g. younger women considering donor egg), the cost/benefit analysis may look very different. To learn more, see our lesson on the subject here.

Again, the costs to do IVF with donor eggs can vary dramatically by the region in which you’re treated and even within that region, the type of donor you select and the third parties you work with.

The above analysis assumes an equal chance of success across all donor eggs. In reality, this is not true. Most donor eggs come from egg banks with variations in quality of eggs and costs. When considering egg donation, it's important to recognize that eggs routinely come from banks rather than clinics. Yet, the quality, sources, costs, and guarantees of these banks can vary. Prospective donors and recipients should conduct thorough research to understand these factors before finalizing any egg donation arrangements.

As for using donor sperm or a gestational carrier, both can dramatically improve the odds of a live birth and tend to warrant the costs they drive.

Fertility Treatment Drugs

Most fertility treatment drugs involve the use of oral medication (e.g. clomiphene or letrozole) or injectable hormones, known as gonadotropins.

Unlike oral medications which tend to be low-cost in nature, injectable hormones can be incredibly expensive.

Drug Type & Dosing

IUI

In the case of IUI, for many patients, there is a benefit to taking drugs. However, as you can see from the data below, taking oral medications like Clomid (clomiphene) or Femara (letrozole) approach IUI with gonadotropin success rates but with lower costs (in the U.S. context) or risk of delivering twins or triplets (“multiples”).

Summary of IUI Drug Profiles

If your doctor wants to do an IUI cycle with gonadotropin,in addition to discussing the medical risks of a multiple birth, you may want to broach the trade-offs of substituting some or all of the gonadotropin with less expensive oral medication.

IVF

As for IVF, typically the more eggs retrieved, the higher the odds of success, as you can below. However, that’s true only up to a point—after retrieving 15–20 eggs, per-cycle IVF success rates plateau. As a result, for some patients (e.g. “high responders”) prescribing ever higher doses of gonadotropin (to produce more eggs for retrieval) doesn’t improve success rates, but will drive up costs (and medical risk, in the form of hyperstimulation).

Live Birth Rate & OHSS

As a result, many doctors tend not push the dosing for “high responders” (who are sensitive to gonadotropins and thus will produce a lot of eggs on lower doses) or for “poor responders” who are distinctly less-sensitive to the drugs and for whom more drug does little to improve success rates (see below).

Poor Responders

However, as you can see in our course on protocols here, there often is a minimum threshold of gonadotropin that needs to be taken so as not put the patient at a meaningful disadvantage. In the eyes of many, that threshold is around 150 IUs per day.

Dose Compared Live Birth Rate

Ultimately, you may want to discuss with your doctor and clinic the medical and financial implications of adjusting your gonadotropin dosing downwards (or upwards), or substituting some of your more expensive gonadotropin for less expensive oral medication. Doctors are more likely to be open to lower doses of gonadotropin if you’re considered a “poor responder” or “hyper responder.”

Gonadotropin Dose & Patient Types

Acquiring Medication

As we mentioned, fertility medication can be costly, especially gonadotropins.

It’s not uncommon for patients to discuss the possibility of acquiring medication legally from regions where the products are perceived to be the same but the prices most certainly are not.

Along a similar vein, in some circumstances, clinics themselves have extra doses or “samples” (provided by the drug company) lying around that they can offer to patients.

Rules and regulations around how and from where a patient procures medication are highly country-specific and need to be consulted along with clinical guidance.

Egg or Embryo Storage

In some countries, and at some clinics, the cost to store eggs or embryos can be substantial. For instance, in the United States, storage costs typically equate to $500–$1,000 per year.

Many patients are reluctant to stop paying storage fees given the sizable up-front (emotional, temporal, and financial) costs already laid out. Also, it can be hard to know when you're definitely done building your family and thus no longer need access to those eggs or embryos.

To illustrate, a person who wants three children, each spaced three years apart, might well find themselves paying annual storage fees (e.g. 10 years x $1,000 per year) that begin to rival that initial IVF cycle (e.g. $15,000–$25,000).

In some regions, third party laboratories offer the ability to store eggs and embryos at a discount (often 50% or less) compared to the cost of on-site storage at a clinic.

In regions where frozen donor eggs are shipped between clinics, the logistical cold-storage infrastructure may be in place for transportation to happen more seamlessly.

However, shipping eggs and embryos likely involves an element of hard-to-quantify risk, not to mention a break in accountability if something goes wrong or those embryos don’t work.

For this reason, we suggest closely probing your clinic’s track record shipping eggs and embryos and the results of thawing and using them upon receipt. Likewise, we suggest asking for the third party’s laboratory’s track record in handling eggs and embryos and whether they go on to be of use.

For context, we suggest you consult our course on laboratory quality with an emphasis on “thaw rates” as well as endpoints like implantation rates, pregnancy rates, or live birth rates.