Reproductive Fertility Specialist
Reproductive Fertility Specialist
Kaiser Permanente Centers for Reproductive Health
Infertility affects 10—15% of people worldwide. While infertility is challenging for anyone who's impacted, people of South Asian heritage may face specific complexities and we’ll address some of those in this course. Let’s start with the basics of fertility treatment.
Generally speaking, there are four ”fertility treatment” approaches, each with their trade-offs on cost, burden, odds of success, and potential risks.
While approaches like “timed intercourse” and “oral medications” are often the least intensive, they’re also the least likely to deliver a baby.
Conversely, approaches like in vitro fertilization are intensive, but (age dependent) dramatically improve the odds of success and for some patients will be the only path to bringing home a child.
We should note, the success rates below reflect data on mostly Caucasian patients in the United States and Europe, and as you’ll see in a later lesson, even in these geographies, success rates can be lower for patients of South Asian heritage. Similarly, costs quoted below reflect quoted prices in the United States, and costs tend to vary dramatically region to region.
For couples trying to conceive naturally, the odds of success rise dramatically if they try during a woman’s “fertile window.” As you can see, trying in the days immediately preceding ovulation raises the odds substantially.
Often, couples believe that “saving up” (restricting the number of days they have intercourse leading up to ovulation) improves the odds of success. However, as you can see from the data below, there’s no detriment in trying more often during the fertile window and clear benefit in trying at least three of the six days leading up to ovulation.
Generally speaking, as you can see below, if a woman or couple hasn’t conceived using timed intercourse after five months, the odds of conceiving each month drops precipitously.
To improve the odds of natural conception, a woman can take oral medications like Clomid (clomiphene) or Femara (letrozole). Taking these drugs improve the odds a woman ovulates an egg that can be fertilized or improves the odds she'll "superovulate" and produce multiple eggs, improving the odds of conception. While the impact on success rates tends to be modest, the cost and burden also tend to be minimal.
While we often lump Clomid and letrozole together, the truth is they are different. Clomid has been studied more extensively but remains in a woman’s system longer. For a sub-group of patients, the distinction does matter: specifically, PCOS patients have better outcomes with letrozole. This may be especially pertinent for women of South Asian heritage because (as you'll see in a later lesson) PCOS is often underdiagnosed, and women of South Asian heritage are more likely to suffer from PCOS than other infertility patients.
After trying to conceive with Clomid or letrozole, for many patients the next step is to try intrauterine insemination. Intrauterine insemination (IUI), sometimes referred to as “artificial insemination,” is the process of placing sperm in a woman’s uterus. This procedure delivers a prepared sample of motile sperm past the vagina and cervix, both potential barriers for sperm, and into the uterus near the fallopian tubes, thereby raising the chances sperm will fertilize a woman’s egg.
While IUI is less intensive than options like IVF (which we’ll cover momentarily), IUI can still require a fair amount of time at a doctor’s office, and the costs can add up. For example, in the United States, the cost of an IUI cycle can range from $500 to $4,000 and depends on which, if any, medications are taken in the lead-up to the insemination (more on that in a moment). In India, IUI costs often range from Rs. 15000—25000.
We have an incredibly detailed course on IUI here that we suggest you look at if this becomes an option you want to consider.
However, IUI success rates are highly dependent on age. As you can see from the data below, success rates go down significantly from ages 35 on, and that is true in most every country where IUI success rates have been published. Below are examples country-wide or from major clinics in the U.S., China, and Japan.
This trend holds true for clinics in India. Below is pregnancy rate data from a single center treating 800+ patients across 2,100+ IUI cycles. As you can see, there was an inverse correlation between odds-of-success and female age.
Yet, even for a woman under the age of 35, the odds are likely that any given IUI will not work. This can be a devastating surprise, and so it’s important to get familiar with the odds of success for IUI.
Given the single-cycle failure rate for IUI, it’s common for women to try multiple inseminations in back-to-back months.
Generally speaking, IUI doesn't help or isn't an option for patients with a low egg supply, advanced maternal age, severely low motile sperm counts, two blocked fallopian tubes, an "inhospitable" uterus due to a few factors (e.g. fibroids, scar tissue, a septum), or gay couples pursuing surrogacy.
IUI success rates and costs vary depending on which, if any, medications are used leading up to an insemination.
The chart below incorporates study data from both China and the United States and shows the correlation of increasingly intensive drugs, higher success rates, but also higher risks (in the form of multiple gestation pregnancies—which can be dangerous both to the mother and child).
To illustrate, if a woman does IUI with no drugs, she may have a 1%–10% chance of delivering a child and if so, a 0%–5% chance that delivery will result in twins. On the other hand, if a woman takes gonadotropin (injectable hormones) leading up to her IUI, there’s a nearly 15% chance she’ll deliver, and if she does, an (extremely high) 30% chance it will be with twins.
There’s the option to do a “natural” IUI cycle, and use no drugs at all, in which case you’ll merely do monitoring to understand when ovulation is likely and have the insemination performed just before ovulation.
The best candidates for this are women with “regular cycles”, meaning they have no ovulatory disorders.
In the data above, these natural cycles had the lowest chances of working, but also the lowest risk of resulting in a multiple gestation pregnancy like twins, triplets, or more.
The next level up are the medications most commonly used with IUI. These are oral medications like Clomid (clomiphene) or letrozole (which also goes under the brand name Femara). These medications are fairly easy to take, inexpensive, and they do boost success rates per cycle into the low teens.
However, the chances that a resulting pregnancy is a multiple gestation pregnancy also rise.
Finally, taking these medications will probably step up the logistics involved in a cycle, because it’s more likely that your doctor will have you come in for monitoring appointments to ensure the medications are working properly—this is more time consuming and also adds some cost.
Generally speaking, many doctors are comfortable performing an IUI with these drugs: they feel the improved odds of success compensate for the increased (but still “tolerable”) risk, cost, and inconvenience.
Finally, the most intensive medications are gonadotropins—these are injections that are expensive (around $2,000 per cycle in some countries like the U.S. and far less in many other regions).
They moderately increase success rates above letrozole (Femara) or Clomid, but in many countries, it’s rare that they would be recommended for IUI, because they are often more costly, and some studies show they drive up the risk of a multiple gestation delivery.
However, we should point out many clinics in India still routinely combine IUI with gonadotropin, and indeed, some report far lower "multiple gestation" pregnancy rates than is recorded in the literature elsewhere. Those doctors suggest to us the reason might be because they put their patients on gonadotropin for a brief 3—5 day window. Before starting an IUI cycle with gonadotropin, it's important to have a detailed discussion with your doctor about the heightened risks involved.
IVF, or in vitro fertilization, is a more intensive and expensive treatment option than IUI—it requires that eggs are surgically removed from the ovaries, that those eggs are inseminated with sperm in a laboratory, and that a resulting embryo is placed in a woman’s uterus with the hopes that it implants and leads to a healthy baby.
A person or couple might strongly consider IVF if:
They are mostly focused on getting pregnant as fast as possible (though by no means is IVF likely to work quickly)
IUI has not previously worked in the first 3–5 or so attempts
There is a medical condition (like blocked fallopian tubes) that renders IUI ineffective
A male partner suffers from “male factor infertility” and upon semen analysis, produces a “total motile count” (number of moving sperm) below 5—10 million
Fertility treatment is needed and the hope is to have multiple children, across multiple pregnancies. IVF may allow patients to create and freeze multiple embryos for future use
A woman has already frozen her eggs, and thus, completed the most expensive and intensive portion of the IVF process
There is a known genetic condition and a desire to minimize the risk of transmission to future children
There have been multiple pregnancy losses due to genetic abnormalities
IVF tends to be performed differently in each country but one universal truth is that, generally speaking, success rates tend to correlate closely with female age. To illustrate, below is data from regions where some clinics report or publish their success rates (we'll note capturing peer-reviewed data from South Asia on an age & cycle-start basis has been difficult). Within each region, IVF success rates coincide with female age.
When British investigators looked at historical data, they noted more than half of women under age 40 deliver a child after three IVF cycles, whereas for women over the age of 40, rates of IVF success tend to be much lower.
As you’ll see below, when “donor eggs” are incorporated into the process, success rates climb quickly.
The U.K. data reflects the reality for egg donor recipients in India as well. According to nationally collected NARI data, the rate of pregnancies per transfer has hovered between 50%—60% on a regular basis.
While in the United States it can be immensely difficult to find donors of South Asian heritage, in India, the number of annual donor-egg IVF cycles is in the thousands and has historically grown each year. That said, the rules around donor egg use is likely to remain fluid.
When a male partner has an underlying fertility issue, “donor sperm” tends to improve success rates, as you can see in the U.K. data below. Unlike in the United States, both egg and sperm donation arrangements in India are required to be anonymous.
If a female partner has difficulty conceiving or carrying with embryos that appear to be of good quality, having a gestational carrier or surrogate also dramatically raises the odds of success, as you can see in the Indian data below. However, we should highlight the legality of using a gestational carrier in many countries (e.g. India) can be a fluid situation and requires continual monitoring.
As we mentioned, IVF is practiced differently in many parts of the world, but generally speaking, there are a handful of basic steps (and decisions) involved. We’ll summarize those below, but if you want the full set of details, head to our comprehensive guide to IVF here.
A woman is usually given injectable hormones to make her ovaries develop as many eggs as they can (say, 8–20) instead of the usual 1–2 that would be matured each month. This continues for an average of 10 days, until a “trigger shot” is taken to start the ovulation process where eggs become mature.
Eggs are surgically retrieved from the ovaries, and typically anesthesia is used during the procedure. A doctor usually uses a vaginal ultrasound to guide a needle that suctions out each egg.
Over the next 3–7 days, a fertility clinic’s laboratory will take all of the collected, mature eggs and try to grow them into healthy embryos.
First, they fertilize the eggs with sperm either by surrounding an egg with sperm in a petri dish, or using ICSI, a micro-procedure where a single sperm is injected into an egg.
Then the laboratory will try to grow the embryos into either Day 3 “cleavage stage” embryos or heartier Day 5, 6, or 7 “blastocyst stage” embryos. Growing embryos to “blastocyst stage” is challenging, and depending upon the region, it can be more common (e.g. United States, Singapore, urban regions of India) or less common (e.g. rural parts of India, China, Europe) to find clinics able to do so.
Once embryos have reached the blastocyst stage, there is an option to remove a few cells and have them sent out for genetic testing, sometimes referred to as PGT-A, PGT, or PGS screening. This testing can either test for a single genetic disorder that runs in your family history or testing can predict if an embryo is likely or unlikely to lead to a healthy pregnancy.
As you can see, implantation rates per embryo transfer are higher with PGT-A tested and approved embryos than they are with untested embryos and are less likely to lead to a miscarriage.
PGT-A is still the exception in IVF procedures given its cost and, to a lesser degree, the local shipping infrastructure required (samples of the embryo need to be frozen and then shipped from the clinic to a "reference laboratory").
Credible experts disagree on the utility of PGT-A screening. For instance, below is data collected from clinics on three continents that reflects PGT-A has less value in younger patients. Where there is more agreement is the value of PGT-A to screen out embryos that carry a specific genetic disorder. We go into more detail on the topic to help you make your decision in our dedicated course here.
After developing embryos, whether or not genetic screening has been done, more clinics and patients are using the option to freeze all of their embryos. Then embryos will be transferred later on.
As you’ll see, according to a small amount of data from the United States, when women of South Asian heritage opt to freeze their embryos and wait (a month or so) to transfer, disparities in success rates may dissipate between women of South Asian and European heritage. However, there are drawbacks to freezing all embryos, and some experts believe it's still preferable to try a "fresh" embryo transfer first, unless patient-specific tests during the cycle indicate otherwise.
An embryo will be transferred into the uterus with the hopes that it “implants” and leads to a healthy pregnancy. The safest option is to transfer one embryo at a time. As you can see in the data below, multiple gestation pregnancies raise the risk to both the person carrying the pregnancy and to the offspring.
For this reason, in most every country there is a push to reduce the number of embryos transferred per transfer. We have a detailed lesson on the subject here, and patients should have a thorough discussion with their doctor of the risks and tradeoffs if the plan is to transfer more than one embryo at a time.
Any embryos of reasonable quality that were not transferred will be frozen and can be used later, either in the event that the first transfer doesn’t work, or if it does work, for more children in the future.
In some senses, you can think of IVF like a funnel. Unfortunately, not every developed ovarian follicle will contain a mature egg, and not every mature egg will lead to a healthy embryo or a baby. At each stage throughout the process, you’ll lose something. That’s why the goal is to have a high number of eggs to start off with. Below is a sample summary of this funnel.
IVF prices vary dramatically by region and whether a local government or insurer covers some of the cost. In regions where patients pay for IVF “out of pocket”, costs can stretch from a few thousand dollars (e.g. in Thailand, Vietnam) to upwards of $20,000 in the United States.
In India, costs typically come in at roughly INR 2,50,000 to 4,00,000 per IVF cycle. Prices can be lower if recombinant gonadotropin is substituted out for urinary gonadotropin. Prices will rise if PGT-A is used.
It’s common for patients to pay significantly more for treatment than the figures quoted by a fertility clinic. Often these quoted prices exclude the prices for required drugs (which can be meaningful) or “add-ons” (e.g. ICSI or embryo testing) the clinic may later insist upon.
To showcase in an American context how drugs and add-ons can change the total cost for each cycle, below is a chart of what patients pay in a handful of U.S. cities.
In countries like India and the U.S., it's rare to have health insurers cover the cost of IVF. If coverage does exist, a woman or couple may be asked to try a progression of timed intercourse, oral medication, and IUIs before receiving coverage for IVF.
Generally speaking, IVF costs and coverage vary. In many countries, a woman or couple will be asked to try multiple (less expensive) IUIs before IVF can be covered. Even if IVF is covered, certain aspects of the process (e.g. drugs, fertilization techniques, tests, ability to transfer multiple embryos at once) may not be. Finally, in many countries where IVF is covered, there can be lengthy delays to receive treatment, and oftentimes, a cap on female age, often 40–45, whereafter treatment won’t be covered.
We think there are a handful of criteria in determining whether one should start with IUI or IVF. We elucidate the factors below, though of course prioritizing those factors is a personal choice.