The choice of older women: Should they do preimplantation genetic testing?

Author: Huang Ying, First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Cai Xiaojing The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Qin Rujuan, The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Qin Yanju The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Reviewer: Zhang Huiqin, Chief Physician and Professor, First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

With the development of society and the liberalization of fertility policies, the proportion of older women becoming pregnant has further increased. However, in 2012, the Canadian Society of Obstetricians and Gynecologists pointed out in its report on delayed childbearing[1] that the natural pregnancy rate of women decreases with age, and when they reach around 46 years old, the natural pregnancy rate basically approaches 0; the spontaneous abortion rate of pregnant women aged 35 to 45 can reach 40%, and that of women over 45 is 60% to 65%; in terms of live birth rate, the live birth rate of women aged 38 to 40 is 19.2%, which rapidly drops to 12.7% for women aged 40 to 42, 5.1% for women aged 43 to 45, and only 1.5% for women over 45[2].

Therefore, while older women are actively preparing for pregnancy, they also face the difficulty of getting pregnant.

Figure 1 Copyright image, no permission to reprint

The three main elements for a successful pregnancy are: good eggs, fertile "soil", and good sperm.

After the age of 35, most women's ovarian function begins to "go downhill", and the decline in ovarian reserve function leads to a decrease in the number and quality of eggs. Among them, the reduction in the number of eggs can directly affect the pregnancy rate, while the decline in egg quality can easily cause egg aging and apoptosis, increase chromosomal abnormalities, and lead to an increase in infertility and miscarriage rates in older women.

In addition, the reproductive environment of older women deteriorates, and the "land" for embryo implantation is not fertile enough or is affected by disease. For example, multiple uterine curettages lead to thinning of the endometrium and poor uterine receptivity, as well as the high incidence of endometriosis, adenomyosis, uterine fibroids, fallopian tube inflammation and other diseases, all of which will cause their infertility rate to increase.

Of course, in addition to the egg quality and quantity of older women and the embryo implantation environment, the impact of sperm quality and quantity on pregnancy cannot be ignored. Male aging, bad living habits, high work pressure and underlying diseases can also lead to a decline in sperm quality and quantity.

Figure 2 Copyright image, no permission to reprint

The risk of spontaneous abortion for women aged ≥35 years begins to increase significantly, and the pregnancy rate and live birth rate decrease significantly. The main reason is the increased incidence of chromosomal aneuploidy (i.e., the number of chromosomes in the chromosome set is increased or one or more chromosomes are missing). All lethal chromosomal abnormalities can lead to miscarriage, such as the increase of polyploidy (such as triploidy and tetraploidy) and the increase of most aneuploidies (monosomy, trisomy, polysomy).

At the same time, advanced female age can lead to an increased incidence of congenital malformations in the fetus, including chromosomal diseases and multi-gene genetic diseases.

Therefore, older women often need the help of assisted reproductive technology.

The American College of Obstetricians and Gynecologists recommends that women aged 35 years or older can try to conceive naturally. If they fail after 6 months, they should receive evaluation and assisted reproductive treatment as soon as possible. Women aged 40 years or older should receive evaluation and assisted reproductive treatment immediately.

When older women go to an assisted reproductive center, the question they often ask is whether they need to undergo preimplantation genetic testing?

Figure 3 Copyright image, no permission to reprint

What is preimplantation genetic testing?

Preimplantation genetic testing refers to the technology of performing genetic testing or chromosome number and structural abnormality testing on embryos before implantation into the mother's uterus during conventional IVF treatment, selectively implanting normal embryos, and preventing the birth of children with single gene diseases and chromosome abnormalities. This technology is mainly suitable for patients with chromosome abnormalities, single gene genetic diseases, unexplained recurrent spontaneous abortions and recurrent implantation failures, and advanced age.

Whether to choose to undergo preimplantation genetic testing and whether a successful pregnancy can be achieved are often individualized choices made by doctors based on the patient's condition, patient wishes, ovarian reserve function, and embryo quality.

Case sharing:

Ren, a 40-year-old woman from Zhejiang, came to the hospital for consultation because she wanted to have a second child. After questioning, it was learned that she had a history of two fetal arrests (one uterine evacuation and one non-uterine evacuation) during her preparation for the second child. She was worried about another natural pregnancy and wanted to do preimplantation genetic testing. After understanding the situation, the doctor asked the patient to undergo an ovarian function assessment. The bilateral ovarian antral follicle count was greater than 10, and the ovarian reserve function was normal. Afterwards, the genetic counselor considered her advanced age and history of adverse pregnancy and recommended preimplantation aneuploidy testing (PGT-A).

For the ovulation induction program, we chose the commonly used antagonist program. After 10 days of continuous medication, we finally obtained 15 eggs, 8 embryos were fertilized normally, two blastocysts were developed and sent for biopsy, and finally only one euploid embryo (4BA) could be transplanted.

Considering the preciousness of the embryo, a down-regulation hormone replacement program with a high success rate was selected during the frozen embryo cycle. Ten days after the embryo transfer, the patient was examined at a local hospital, and the human chorionic gonadotropin (HCG) was 188 mIU/ml. After more than one month of pregnancy preservation, the fetal heart and embryo bud were already visible, and the obstetrics file was established.

For women like Ren, who have normal ovarian reserve function, only one blastocyst can be transplanted during preimplantation genetic testing. So, if it is an older woman with diminished ovarian reserve function, can she still choose preimplantation genetic testing?

Figure 4 Copyright image, no permission to reprint

Clinically, older women, especially those with low ovarian reserve function, often face the embarrassment of having few available embryos, failed ovarian culture, or no available embryos for transplantation after screening. At the same time, they also need to bear the economic burden of preimplantation genetic testing.

The "Clinical Practice Guidelines for Assisted Reproduction for Older Infertile Women in China" recommends that older women aged ≥38 years or with a history of repeated implantation failure or repeated spontaneous abortion may consider preimplantation genetic screening.

Therefore, older women need to look at preimplantation genetic testing technology rationally and carefully understand its pros and cons during genetic counseling.

References:

[1]Johnson JA, Tough S, SOGC Genetics Committee. Delayed child bearing[J]. J Obstet Gynaecol Can, 2012, 34(1): 80-93.

[2] Chinese Society of Reproductive Medicine. Clinical practice guidelines for assisted reproduction in elderly infertile women in China[J]. Chinese Journal of Evidence-Based Medicine, 2019, 19(3): 253-266.