What Is the Best Fertility Treatment for Low Ovarian Reserve?
Diminished ovarian reserve (DOR, also called low ovarian reserve or low egg reserve) is a condition where a woman has a low number of high-quality oocytes in her ovaries.1 Many women who have diminished ovarian reserve with high follicle stimulating hormone (FSH) and/or low anti-Mullerian hormone (AMH) are told that donor eggs are their only treatment option. At CHR, almost all of our patients with diminished ovarian reserve have been told by other fertility centers that their only chance of having a baby is with donor eggs.
However, about one third of these patients do get pregnant with their own eggs after receiving appropriate, thoroughly individualized treatment for diminished ovarian reserve at CHR. Although pregnancy rates with IVF are certainly low for patients with DOR, we have achieved better pregnancy rates than the “less than 1% chance” often quoted to these patients.
At CHR, we have focused our reproductive medicine research and treatment on women over 40 and young women with premature ovarian aging (POA, an early-onset form of DOR) for close to two decades. Our physicians and scientists have made many breakthroughs and refined our treatment approaches, as evidenced by dozens of research studies published on this topic. A recent analysis of our IVF outcomes in "poor-prognosis" patients has shown that the "less than 1% chance of pregnancy" given to so many women with high FSH levels or low AMH levels is often incorrect. Even with severe DOR, some women do have a better chance of pregnancy with their own eggs than they’ve been led to believe.
With this experience under our belt, we are convinced that many women with even very low ovarian reserve can conceive with their own eggs.3 We provide individualized treatment tailored to each woman’s ovarian reserve status as well as any accompanying conditions affecting her fertility (like endometriosis or immunological issues). Ultimately, time is the most important factor with DOR treatment. The sooner a patient’s treatment can be started, the better her treatment options and the higher her pregnancy chances.
Diagnosing Diminished Ovarian Reserve: AMH, FSH, and Other Indicators
Diminished ovarian reserve is diagnosed by evaluating specific hormone levels through ovarian reserve testing. Blood tests are used to measure levels of key hormones including AMH and FSH. AMH can be measured anytime in the menstrual cycle, while FSH needs to be measured early on in the cycle (typically cycle day 3). AMH and FSH are among the most important hormones for assessing female fertility in many situations: for young women considering fertility preservation, for women who have been trying to get pregnant, and for women who are poor responders to IVF.
Some fertility centers also use antral follicle count (AFC) to measure functional ovarian reserve. Follicles are tiny sacs in a woman’s ovaries that hold the developing oocytes. Antral follicle count is measured by looking at the number of antral follicles in the woman’s ovaries using transvaginal ultrasound. This test is performed during the first week of the menstrual cycle, typically between cycle day 2 and cycle day 5.
However, we find it most useful to focus on age-specific levels of AMH and FSH. Many centers neglect to consider age when they evaluate hormone levels, which can lead to misdiagnosis (or a missed diagnosis). At CHR, we have developed age-specific hormone charts that enable us to be more accurate in defining the cause of infertility for women who are having problems getting pregnant naturally -- as well as women who are poor responders to IVF. With precise diagnosis, we can then provide highly personalized treatment.
Other hormones used in the infertility testing workup include estradiol, which is important because this hormone suppresses the FSH levels. Some fertility centers also test inhibin B. Uniquely at CHR, we also recommend testing for the FMR1 gene. This is typically associated with fragile X syndrome, and it has been known for a long time that some women with high CGG counts on this gene can develop premature ovarian failure. At CHR, we’ve identified the CGG counts on the FMR1 gene to be a predictor of future ovarian reserve.
Low Ovarian Reserve and Natural Pregnancy
When trying to start a family without the use of fertility treatment, DOR and natural conception are at odds with each other. DOR usually means that a woman just does not have the supply of good-quality oocytes (immature eggs in the follicles) she needs for ovulation and fertilization without medical assistance. It’s important to remember that time is always of the essence when trying to get pregnant with low ovarian reserve.
The CDC and professional organizations in our field recommend that women over 35, who are at higher risk of DOR, consult a fertility specialist when they do not get pregnant after 6 months of unprotected intercourse.2 This 6-month timeline is shorter than the 12-month timeline recommended for women younger than 35, due to the urgency associated with treating DOR--women over 35 shouldn’t wait longer than that to get tested and receive medical advice.
Low Ovarian Reserve and Intrauterine Insemination (IUI)
Some IVF centers recommend intrauterine insemination (IUI) to patients with low ovarian reserve. This is a form of fertility treatment where prepared sperm is directly injected into the uterus. In CHR’s opinion, IUI is not the best fertility treatment for DOR. The often-cited claim is that patients with DOR have “less than 1 % chance of pregnancy” with IVF anyway, so they might as well try multiple rounds of less costly IUI, rather than going straight to costlier and more involved IVF treatment. But this is highly inaccurate and goes against the published evidence in the literature. In our experience, IVF that is designed specifically for each DOR patient has a much higher success rate than IUI in women with DOR.
Importantly, going through multiple unsuccessful IUI cycles with low ovarian reserve also leads to wasted time. With declining ovarian reserve, 3-6 months can make a significant difference. By the time patients move to IVF after many months of failed IUIs, they may face lower pregnancy chances with IVF than if they had started IVF treatment straight away. Some insurance policies require IUIs before patients can access their IVF benefits, and we feel this is against the best interest of patients.
At CHR, once ovarian reserve testing reveals that a patient has diminished ovarian reserve, our physicians usually recommend that patients start ovarian preparation and move onto IVF as soon as possible to ensure the best chance of pregnancy. We are serious about the time-sensitive nature of fertility treatment to maximize fertility potential. We stayed open for urgent treatments during the COVID-19 closures for this reason, and this is also why we will always recommend the treatment that won’t waste precious time.
DOR and In Vitro Fertilization (IVF)
For most women with DOR looking to get pregnant with their own eggs, IVF with ovarian stimulation is the quickest and most reliable treatment option.4 With our specialized IVF protocol for low ovarian reserve, women with DOR are given different treatment plans than younger women with normal ovarian reserve. For instance, these patients need larger doses of fertility medications to produce a good number of good-quality eggs.
Women with DOR also need to prepare their ovaries before starting stimulation. For over a decade now, CHR has been giving women DOR a supplement of dehydroepiandrosterone (DHEA) before starting the IVF cycle. We do this in order to readjust their ovarian environment to a more youthful, androgen-rich one. This approach using dehydroepiandrosterone, which was first developed at CHR, allows oocytes to undergo a healthier maturation process, and it has proven a life-changing treatment. Our experts have shown that well-designed IVF for DOR patients can increase the expected pregnancy rate for women who previously thought they wouldn’t be able to have a baby using their own eggs.
DHEA as a Treatment for Diminished Ovarian Reserve
Dr. Norbert Gleicher discusses how DHEA can be used to improve egg quality and quantity in DOR patients.
ICSI for Diminished Ovarian Reserve
Some patients ask us whether ICSI (intracytoplasmic sperm injection) is a better treatment option for women with DOR than traditional IVF. ICSI is a form of IVF where best sperm are selected and injected directly into each egg, rather than having sperm find and fertilize eggs in a petri dish like in a traditional IVF cycle. Though ICSI is most known as a treatment for male factor infertility, it is also a good strategy for maximizing pregnancy chances for women with DOR who produce a low number of eggs for IVF. Because it ensures as many eggs as possible are fertilized with the best-quality sperm, ICSI can help improve the number of embryos available for transfer, greatly improving expected pregnancy rates and live birth rates.
Finding the Best Diminished Ovarian Reserve Treatment
Timing is everything when it comes to diagnosing and effectively treating diminished ovarian reserve. There are conflicting treatment approaches for DOR, some of which are better-supported by evidence than others. And it can sometimes be difficult for patients to figure out whom to trust, or whether the current treatment path is the right one. CHR's DOR experts can help you throughout your decision-making process.
We hope you will decide to start your journey on the right foot, consulting our physicians and undergoing a thorough infertility workup, including ovarian reserve testing. But we are here to help you find the right treatment even if--or especially if--you have already experienced disappointments elsewhere.
Patients who are already receiving treatments at other fertility centers can also take advantage of our online second opinion consultation. In this consultation, you will be able to share the results of your previous fertility blood tests and discuss your infertility condition and treatment options with a CHR reproductive endocrinologist.
1. Gleicher, N. Barad, D. Weghofer A. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. Link. Published February 7, 2011. Accessed August 21, 2020.
2. What is Infertility? - Reproductive Health - CDC, Centers for Disease Control and Prevention. Link. Page last reviewed: April 17, 2020. Accessed August 21, 2020.
3. Gleicher, N. Barad, D. “Ovarian age-based” stimulation of young women with diminished ovarian reserve results in excellent pregnancy rates with in vitro fertilization. Reprod Biol Endocrinol. Link. Published December, 2006. Accessed August 21, 2020.
4. Gleicher, N. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol. Link. Published May 17, 2011. Accessed August 21, 2020.
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.