The ovarian reserve is the quantity and quality of eggs a patient’s ovaries can produce. Diminished, or low reserves occur naturally with age as the ovaries lose their reproductive potential leading to reduced fertility. Although this process is completely natural it can also affect younger women in some cases.
We invited Professor Evangelos Papanikolaou, the co-founder of the Assisting Nature IVF clinic in Greece and a world-renowned infertility expert to explain what fertility specialists do to combat this issue and what options are available for patients with such a diagnosis. He does so by using the examples of four real-life cases he encountered in his professional experience.
The first case Professor Papanikolaou describes is that of a 44-year-old woman, recently married, who experienced two miscarriages from natural conception. Her first IVF cycle failed during the implantation stage – despite being able to produce two blastocysts, the implantation did not result in a pregnancy. As the patient didn’t accept hormones for further stimulation, professor Papanikolaou decided on a natural IVF cycle – that is to say, a cycle without hormonal stimulation – in order to create as many embryos as possible, which were then put through PGS testing. Following nine natural cycles, the embryologists were left with 7 day-3 embryos, which then were tested.
The results of the test, however, revealed the cause of the repeated failure – all seven embryos were aneuploid, or chromosomal abnormalities. Faced with such results, the patient decided to undergo a fresh egg donation cycle, resulting in a successful pregnancy concluding with the live birth of a healthy child. Two years later, the patient underwent another egg donation cycle, this time using frozen cells, which also resulted in a child.
The second case concerned a 30-year-old patient with a very low AMH – 0,1 ng/ml. Following two failed IVF cycles in a different clinic, she decided on a third attempt under the care of prof. Papanikolaou. Following another stimulation cycle, no eggs were able to be retrieved.
Following the result, a decision was made to undergo natural cycles in order to accumulate embryos; four such cycles resulted in a single egg being retrieved during one of the cycles. After it was fertilised and implanted, the pregnancy did not take hold. It was obvious that pregnancy using the patient’s own eggs wasn’t an option; therefore, she agreed to an egg donation cycle, which resulted in a successful pregnancy on the first attempt. At age 31, she gave birth to twins.
Patient number three was also young – diagnosed with infertility at 27 years of age, she began attempting to conceive using IVF two years later. Her AMH was similarly low to patient #2 – below 0.3 ng/ml. Her first cycle, using ovarian stimulation, resulted in one healthy blastocyst, which unfortunately did not result in a pregnancy.
The second attempt, then, was made with the goal of freezing every embryo that could be generated; it turned out only one embryo was generated, which was then vitrified. Before it could be tested and implanted, however, the patient became spontaneously pregnant! The pregnancy resulted in the successful delivery of a healthy child. As you can imagine, this is the best possible scenario for an infertile patient.
The fourth case Professor Papanikolaou described was that of a 42-year-old woman suffering from polycystic ovary syndrome (PCOS). She did, however, have regular cycles. After being diagnosed with infertility half a year prior, she underwent her first IVF cycle with ovarian stimulation and PGS testing. Five blastocysts were generated and biopsied, with two being determined as genetically normal. Following a frozen embryo transfer, the patient became pregnant following just one cycle.
The conclusion can be drawn: low AMH does not differ much from other causes of infertility. There are successful strategies that result in pregnancy. Women with low ovarian reserve and women of an advanced reproductive age face the same difficulties. There are four ways a patient like that can end their reproductive journey: they may undergo egg donation, continue with repeated IVF attempts while utilising techniques such as PGS, get pregnant spontaneously or give up altogether. As you can see, then, the choice is really whether to continue trying with the patient’s own eggs, or whether to use a donor.
Both methods are valid choices, although it really depends on the individual patient and whether or not they are able to produce eggs in sufficient amounts to generate healthy embryos. Some, like patient number two, are not; for them, egg donation would be the only option. It is worth noting that egg donation cycles have around a much higher than own egg IVF cycles, even in the best of circumstances. Oocyte quality plays that much of a role in successful embryo development.
Patients deciding to undergo egg donation often express concerns – what will the child’s character be? Will it resemble me and my partner? What about inheritable diseases? Do I tell my child?
Fortunately, egg donation is very well regulated by law. In most countries the donation process, while anonymous, requires the clinic to match donors and patients using phenotype characteristics (that is, hair and eye colour, race, height, weight etc.), while in some countries additional information may be disclosed, such as education and character traits. Because of that, the child is guaranteed to resemble the parents as much as possible. Donors have also screened for any genetic predisposition towards or carrier markers of genetic diseases; if they are found to be the carrier of any illness which could endanger either the mother or the child, they are disqualified from the donation process. Egg donation patients are also often offered psychological counselling which helps them fully understand the implications of the process.
The screening process deserves to be touched upon in more detail. As Professor Papanikolaous argues, the current tests according to egg donation guidelines aren’t adequate, as family histories of donors are often inaccurate. Genetic carrier screening is the first step in addressing that issue, allowing clinics to determine if the donor is a carrier of congenital deafness, heart defects and other diseases. However, it needs to be stressed that everyone is a carrier of at least five genetic mutations – in the future, as full genetic mapping and screening becomes the norm, it will be readily apparent that “perfect donors” don’t actually exist.
When considering egg donation, choosing a reputable clinic should be the priority. Professor Papanikolaous points out several aspects which patients need to make special notice of when choosing a clinic. First of all, the clinic should only recruit donors with a proven fertility record; that does not only mean the donor has already had children or donated eggs which resulted in children, but also that they are psychologically stable and that they can deal with the responsibility.
Second of all, the clinic should focus on quality, rather than quantity, in their stimulation treatments – although they should aim to receive a reasonable amount of oocytes, they can’t drive their donors into ovarian hyper-stimulation syndrome (OHSS), as it can severely impact the quality of received oocytes. The use of OHSS-free protocols is a must in modern reproductive medicine.
The clinic should also only transfer day five embryos; that is, only those which have reached the blastocyst stage. The use of time-lapse incubators and the availability of PGS testing also indicate the modern quality of service.
Thirdly, the clinic should place a heavy emphasis on investigating the patient’s condition. Hysteroscopies provide a wealth of information to fertility specialists, which makes it puzzling as to why some clinics shy away from them. Professor Papanikolaou’s Assisting Nature clinic recommends hysteroscopy as part of the initial examinations of the patient’s reproductive health. It also allows doctors to perform a uterine scratch in order to boost endometrial receptivity.
The pharmaceutical protocol used on patients should also include doses of aspirin or heparin in order to combat potential thrombophilic effects. Professor Papanikolaou also believes in augmenting the treatment with low doses of corticosteroids to induce more favourable immunologic conditions.
We also got to learn a few insider secrets – here are some things to ask the clinic in order to gauge the quality of their services. First of all, ask them who performs the embryo transfer – some centres train new, inexperienced doctors. As noble as that is, there is a documented difference in pregnancy rates between clinics that only allow experienced staff to perform the transfer and those that don’t.
The quality of the work performed at the embryological laboratory is also worth asking about – is anyone auditing the lab? What are the quality control measures in place? Does the lab submit their results for review to some sort of authority?
And speaking about the lab – what about the vitrification or freezing of cells? It is, after all, an operator-dependent procedure; that means that the results can be wildly different depending on who actually does the deed. Only experienced embryologists should perform the procedure. If you’re interested in a clinic, ask about their survival rates and who performs their vitrifications.
Professor Papanikolaou also tackled a common concern among patients – namely, the quality of the eggs received from donors. According to a study performed in the United States, 65% of eggs received from donors are aneuploid. Some patients who decide on egg donation think it’s going to be a magic bullet that will make them pregnant outright. The data shows that won’t be the case in the majority of cases, however.
IVF is still a game of odds – doctors generate as many embryos as possible with the expectation that at least a third of them will be euploid. Commonly, in egg donation scenarios, oocytes retrieved from a single donor are split between two recipients. With an average of fifteen eggs retrieved per cycle, seven eggs are assigned to a patient, a third of which will result in euploid embryos. This means only one or two viable embryos per cycle! Fortunately, we can skew the odds in our favour using modern testing procedures, such as PGT-A. Unfortunately, genetic testing is not a standard part of embryo selection yet; for now, embryos are still selected using morphological parameters. The falling costs and rising availability of PGT-A, however, may change that in the coming years.
The best way to game the odds, however, is to offer exclusive donors. In order to save time and costs, many clinics offer “1 to 2” donations – that is, a donation is split between two recipients. According to data presented by Prof Papanikolaou, however, simply switching to exclusive donation increases delivery rates from 50% up to even 70%, simply because the embryologists have more materials to work with.
If you think that egg donation treatment is something you are willing to consider, your next step is to choose between fresh or frozen donor eggs. Before you make a decision, you may want to watch another webinar “Fresh donor eggs or frozen eggs for IVF – what’s better?” We also recommend another webinar on ‘Donor eggs – it’s all about quality, no. of eggs & qualification process‘.
YOU MIGHT BE INTERESTED IN
Patients’ Success Stories – Low Ovarian Reserve