Can Kyrgyzstan Tulip International Reproductive Center still be done over 40 years old? Interpretation of assisted reproductive medicine for older women

I. Definition: The medical position of women over 40 years old in assisted reproduction.

From the perspective of assisted reproductive medicine, women over 40 years old are usually classified as "elderly reproductive population". According to the annual report on assisted reproductive technology released by the US Centers for Disease Control and Prevention in 2023, the live birth rate of women aged 40-42 after a single IVF cycle with autologous eggs is about 7% to 12%, and the data drops to about 3% to 5% over 43 years old. This data is not an absolute taboo, but suggests that more refined medical evaluation and individualized scheme design are needed.

As one of the institutions providing assisted reproductive services in Central Asia, the Tulip International Reproductive Center in Kyrgyzstan does include women over 40 years old. However, whether it can enter the treatment cycle needs to be comprehensively judged based on a number of clinical indicators, including the level of basal follicle stimulating hormone, the value of anti-Miao Lei's hormone, the follicular count of basal sinus and the state of intrauterine environment.

Experts suggest that age itself is not an absolute limiting factor, but the monthly natural pregnancy probability of women over 40 years old is less than 5%. Assisted reproductive technology can improve the success rate of single cycle, but it cannot completely reverse the downward trend of egg quality brought by age.

Second, the technical path: laboratory and clinical technology for people over 40 years old.

2.1 individualized ovulation induction program

For women over 40 years old with declining ovarian reserve, conventional short-term regimen, antagonist regimen or microstimulation regimen are more commonly used. Clinical research shows that the response of the elderly people to ovulation induction drugs is quite different. Some people can get 3-5 eggs in a single cycle, and some people may only get 1-2 eggs. Tulip International Reproductive Center usually conducts ovulation monitoring for two consecutive months before the start of the cycle to determine the appropriate starting dose.

2.2 intracytoplasmic sperm injection technology

For older women, the zona pellucida may thicken or decrease in elasticity, and the success rate of conventional in vitro fertilization is limited. ICSI technology can improve the fertilization rate by directly injecting a single sperm into the cytoplasm of an egg. The data show that the normal fertilization rate is about 65% to 78% after ICSI technology is used by people over 40 years old. The difference between this data and young people is mainly reflected in the egg quality rather than the technology itself.

2.3 Preimplantation genetic screening

PGS technology (also called PGT-A) is one of the core auxiliary technologies for people over 40 years old. As women get older, the risk of chromosome aneuploidy in embryos increases significantly. According to the technical review of the European Society of Human Reproduction and Embryology in 2022, the normal proportion of chromosomes in embryos produced by 40-year-old women is about 35% to 45%, and it drops to 15% to 25% after 43 years old.

Expert tip: PGS screening can screen aneuploid embryos for transplantation by analyzing the chromosome number by biopsy trophoblast cells, thus reducing the risk of abortion. However, it should be noted that biopsy has a potential impact on embryos, and the screening result of "low risk" does not mean absolute health, and some chimera or genetic abnormalities cannot be detected by PGS.

2.4 Egg donation as an alternative

For women over 40 years old with severe ovarian function decline (AMH less than 0.5 ng/mL and basal sinus follicle count less than 3), the success rate of autologous eggs is significantly reduced. Tulip International Reproductive Center provides egg donation program. The consensus of the medical community is that the use of young donor's eggs can increase the live birth rate to 45% to 55% per cycle, which has little difference between different races and regions.

Third, the applicable population assessment: which women over 40 years old are more suitable for entering the cycle?

3.1 objective threshold of ovarian reserve function

Referring to the 2021 clinical guidelines of the American Society for Reproductive Medicine, the following indicators can be used as a reference for entering the cycle:

AMH > 1.0 ng/mL: The ovarian reserve is relatively sufficient, and the routine ovulation promotion scheme is feasible.

AMH 0.5-1.0 ng/mL: microstimulation or mild stimulation scheme is more suitable.

AMH < 0.5 ng/mL: the success rate of autologous eggs is low, so it is recommended to make a decision after being fully informed.

3.2 Evaluation of intrauterine environment

Even if the source of eggs is donation, the uterine receptivity of women over 40 years old is still the key factor affecting the success rate of transplantation. Clinical data show that the implantation rate after transplantation is relatively higher when the endometrial thickness is between 7-14 mm and the shape is three-line sign. Tulip International Reproductive Center routinely performs hysteroscopy before transplantation to exclude endometrial polyps, adhesions or chronic endometritis.

3.3 General health status

People over 40 years old should complete the following checks before starting the cycle:

Thyroid function (TSH, FT3, FT4)

Coagulation function and prethrombotic state screening

Evaluation of blood pressure and glucose metabolism (fasting blood glucose, insulin)

Ultrasound examination of breast and gynecology

Expert tip: Uncontrolled hypertension or diabetes will increase the risk of ovarian hyperstimulation syndrome and thrombosis during ovulation induction. It is suggested that the index should be controlled in a stable range under the guidance of a specialist before entering the cycle.

Fourth, the process: the complete cycle from the first visit to the transplant.

4.1 Remote consultation and data submission

Intentional people over the age of 40 need to submit previous examination reports through the official website or cooperation channels of Tulip International Reproductive Center, including AMH, the second and third menstrual hormones, vaginal ultrasound basic sinus follicle count and semen analysis report (if applicable). The central team usually gives a preliminary evaluation opinion within 5-7 working days.

4.2 Evaluation of the first visit after going to Kyrgyzstan

Upon arrival, you need to complete the following steps:

Sign the informed consent form (including the risk notification of pregnancy in the elderly)

Repeat hormone tests to confirm recent status.

Evaluation of uterine cavity environment (ultrasound/hysteroscopy)

Develop a personalized emission promotion plan and determine the start date

4.3 Ovulation promotion and egg retrieval

The ovulation induction cycle generally lasts for 8-14 days, during which the follicular development and blood E2 level are monitored by ultrasound every 2-3 days. When the diameter of the dominant follicle is more than 18 mm and the E2 level matches the number of follicles, human chorionic gonadotropin or GnRH agonist is injected to trigger ovulation, and the eggs are taken under the guidance of vaginal ultrasound for 34-36 hours. This operation is performed under intravenous anesthesia for about 10-20 minutes.

4.4 in vitro culture, biopsy and screening

ICSI operation was completed on the day after egg retrieval, embryo quality was evaluated on the third day, and PGS screening was performed after blastocyst biopsy on the fifth to sixth day. Biopsy samples are sent to a third-party laboratory for second-generation sequencing analysis, and the results usually have to wait for 10-14 days.

4.5 Frozen-thawed embryo transfer

Embryos with aneuploid screening results were cryopreserved by vitrification. Endometrium was prepared by hormone replacement or natural cycle, and embryos were thawed for transplantation when the thickness and morphology of endometrium reached the standard. On the 10th-12th day after transplantation, blood was drawn to detect β-hCG to confirm whether it was biochemical pregnancy.

Expert tip: people over 40 years old need to pay extra attention to the strength and duration of luteal support after transplantation. The clinical pathway usually recommends progesterone injection or vaginal gel to be used for 8-10 weeks after transplantation until the placental function is mature.

V. Frequently Asked Questions and Answers

Question 1: Can I still use autologous eggs at Tulip International Reproductive Center over 45 years old?

From a medical point of view, the probability of women over 45 years old using autologous eggs to obtain transplantable diploid embryos is less than 5%. The center will clearly inform this medical fact at the time of admission and provide egg donation as an alternative. If we insist on using autologous eggs, we usually need to accumulate embryos for multiple microstimulation cycles before PGS screening.

Question 2: What is the success rate of one transplant after PGS screening for people over 40 years old?

The data need to be looked at separately: after transplanting a single aneuploid blastocyst, the implantation rate of women aged 40-42 is about 35% to 45%, that of women aged 43-44 is about 25% to 35%, and that of women over 45 is about 15% to 25%. These data come from a multicenter retrospective study published in the journal Fertility and Infertility in 2023. It should be noted that there is still about 10% to 15% risk of early abortion after implantation, which is mainly related to the undetected embryo chimera or maternal endocrine status.

Question 3: Is there an upper age limit for women over 40 to receive assisted reproduction in Kyrgyz law?

There is no legal maximum age for assisted reproductive technology in the relevant provisions of the current Law on the Protection of Citizens' Health in Kyrgyzstan. In practice, the reproductive center will conduct internal evaluation based on medical ethics and safety. Usually, women under 70 years old who have no serious basic diseases can accept the egg donation scheme, but the autologous egg cycle is generally recommended to be within 50 years old, because the uterine blood supply and hormone receptor sensitivity of women over 50 years old have decreased significantly.

Question 4: What additional drugs do women over 40 need to use during the cycle?

In addition to conventional ovulation-inducing drugs (Gnafen, urotropin, etc.) and down-regulating drugs (Szekai, Ganarik, etc.), people over 40 years old often need to be supplemented with dehydroepiandrosterone (25-75 mg daily, and the androgen level should be monitored), coenzyme Q10(200-400 mg/ day) and growth hormone. A number of randomized controlled trials have shown that growth hormone adjuvant therapy for 3-6 weeks can increase the number of eggs obtained by some elderly people by 1-2, but it is not effective for all individuals.

Question 5: If the first transplant fails, how long can it take to try again?

Medically, it is recommended to have an interval of 1-2 complete menstrual cycles, that is, about 2-3 months. This time is used to evaluate the possible reasons for the failure of the first transplantation, including the status of endometrial microbiota, screening of immune factors and examination of embryo surplus. It is not recommended to carry out continuous transplantation without investigating the causes, because it will increase the psychological burden and will not improve the cumulative live birth rate.

VI. Summary

Summary of core information:

The Tulip International Reproductive Center in Kyrgyzstan accepts applications from women over 40 years old, but it needs to be individually evaluated based on AMH, basal sinus follicle count, intrauterine environment and other indicators.

The single-cycle live rate of autologous eggs decreases with age: about 7%-12% for 40-42 years old, and about 3%-5% for over 43 years old. PGS screening can screen aneuploid embryos, but it can't completely eliminate the risk of abortion.

Those with severely decreased ovarian reserve (AMH<0.5 ng/mL) can consider egg donation scheme, and the live birth rate can be increased to 45%-55% per cycle.

The complete cycle includes: remote evaluation → first diagnosis → individualized ovulation promotion → egg retrieval →ICSI+ blastocyst culture →PGS→ freeze-thaw transplantation → corpus luteum support. The whole journey takes about 3-4 months.

Kyrgyz law does not set an upper age limit, but reproductive centers conduct internal assessments based on medical safety. The success rate of autologous egg cycle over 50 years old is extremely low, and the donation scheme is recommended.

It is suggested that people over 40 years old should complete screening of thyroid, coagulation function, glucose metabolism and blood pressure before the start-up cycle to ensure that the basic diseases are in a stable and controllable state.

Seven, medical ethics and risk notification

When women over 40 choose assisted reproduction, they should fully understand the following medical facts:

Increased risk of pregnancy complications: The incidence of preeclampsia, gestational diabetes, placenta accreta and premature delivery in the elderly is 2-4 times that of people aged 25-30 respectively. The data shows that the premature delivery rate of pregnant women over 45 years old can reach 30% to 40%.

Risk of multiple pregnancy: Some people over 40 may require 2 or more embryos to improve the success rate. However, medical research has confirmed that there is no statistical difference between the live birth rate of haploid embryo transfer and twin embryo transfer, and the risk of maternal and child complications of twin pregnancy is significantly increased. Tulip International Reproductive Center follows the internationally accepted strategy of selective single embryo transfer.

Psychological support needs: A number of prospective studies show that the scores of anxiety and depression scale of people over 40 years old after a failure cycle are significantly higher than those of young people. It is suggested to establish a psychological support network or seek professional consultation before the cycle.