Protection and preservation of reproductive capacity

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Qiao@263.netAbstract: This article from the concept of fertility and ovarian reserve evaluation and influencing factors of reproductive capa


Abstract: This article from the concept of fertility and ovarian reserve evaluation and influencing factors of reproductive capacity, protection and preservation, research progress on protection and preservation of the female reproductive ability reviewed and biological safety and medical consultation etc..

Key words: reproductive capacity; ovarian reserve; reproductive capacity protection; reproduction

Capacity preservation; biological safety; medical consultation

CLC number: R71 document code: C

Abstract:This review focuses the definition offertility, ovarian preservation its impact preservation; protection and of female fertility, safetyissue and clinical consulting. factors (and)

Keywords:fertility; ovarian preservation; fertility

Protection; fertility preservation; safety issue; clini-

Cal consulting

Reproductive capacity includes female reproductive capacity and male reproductive capacity

The ability to conceive and reproduce in the female reproductive system, which refers to the male reproductive system

Including the oocyte and sperm fertilization, maternal conception and

The process of childbirth offspring. This article focuses on the protection of female reproductive capacity


1 Evaluation of ovarian reserve

Ovarian reserve refers to the growth and development of ovarian follicles

The ability of mature oocytes is the most important factor affecting female reproductive capacity

Independent factors. The main purpose of the evaluation of ovarian reserve is to determine ovarian reserve

Whether or not significantly reduced reproductive capacity. Current methods for evaluating ovarian reserve

There are many.

1.1 age was a direct indicator of ovarian reserve. Ovarian reserve

With the increase of age, physiological decline after the age of 30, the trend is more clear

Obviously, reproductive ability began to lose after 40 years of age, around the age of 50 reproductive capacity


1.2 monitoring methods mainly refers to the determination of serum hormones and cytokines levels, such as

Serum follicle stimulating hormone (follicle stimulating hormone, FSH), Huang Tisheng

Hormone (lutropin, LH) and LH/FSH levels, estradiol (oes-)

Tradiol, E2), anti Mullerian hormone (anti-M llerian hormone, AMH),

Inhibin B (inhibin-B) level, antral follicle count (antral folli-)

CLE count, AFC), ovarian blood flow, ovarian volume and mean diameter.

1.3 ovarian stimulation test commonly used clinical clomiphene stimulation test (CCCT),

Exogenous FSH stimulated ovarian reserve test (exogenous FSH ovarian re-)

Serve test, EFORT) and gonadotropin releasing hormone stimulation test (Gn-)

RH-agonist stimulation test, GAST) indirect evaluation of ovarian reserve function.

In addition, the initial response of the IVF to the gonadotropin in the treatment cycle is also

Reflects its ovarian reserve.

1.4 although the ovarian biopsy can directly detect the density of ovarian follicles,

However, the method of injury to some of the follicles, causing trauma to patients, is not recommended


The sensitivity of this method was 39% to 97%, and the specificity was from 50% to

96%, and any kind of test method to evaluate the ovarian response, especially the ovary

There is no uniform standard for adverse reaction, and the evaluation of ovarian reserve is also very large

Complexity and variability. There is no universally accepted method for the detection of ovarian reserve,

Flexible combination of clinical biochemical indicators, morphological indicators and functional indicators, in order to achieve better results.

2 influencing factors of ovarian function

2.1 genetic factors X chromosome interlocking gene and autosomal dominant group

Due to participate in the regulation of ovarian function, has found that about 25 genes, these

The abnormal gene may cause ovarian function decline or premature ovarian failure (prema-

Ture ovarian failure, POF). X chromosome linkage gene abnormality has X

Monomer, X trisomy, partial deletion or ectopic X chromosome and fragile X, etc.

Autosomal dominant genes such as FSH, FSHR, LH, LHR, GDF-9, inhibin A,

GALT, AIRE, NOGGIN, POLC and other genes can be induced when abnormal

The number of primordial follicles decreased, the follicle apoptosis increased, and the follicle maturation disorder

Decreased ovarian reserve and decreased reproductive capacity.

2.2 autoimmune factors: abnormal recognition of the immune system

T cells or NK cells and cytokines mediate autoimmune diseases

Injury, promote follicular apoptosis, reduce ovarian reserve.

2.3. The incidence of POF is associated with the infection of mumps

2% to 8%. The incidence of POF has increased in recent years

Plus. Other infections such as cytomegalovirus, herpes simplex virus, malaria, Shigella

Sex can damage the development of ovarian follicle.

2.4 hydroxylase deficiency and abnormal metabolism of 17- GALT can cause female primary


2.5 physical and chemical factors

2.5.1 radiation injury in patients with ovarian cancer treated by radiotherapy

Radiation damage was caused by the age of patients, the location of irradiation and the amount of radiation

Vary. Patients under 40 years of age had a stronger tolerance to radiation injury, 20Gy radiation

Can cause ovarian failure, and older, 6Gy can cause ovarian failure

Exhaustion (1). The effect of abdominal radiation therapy on reproductive function in children

Not only can cause infertility, but also directly affect the outcome of pregnancy, spontaneous abortion,

Intrauterine growth retardation, premature birth and low birth weight infants increased (2).

2.5.2 chemotherapy drugs for cancer, autoimmune, or hematological diseases

The patients need to be treated with chemical drugs, and the damage of the ovarian function depends on the degree of suffering

Age, toxicity and dosage of chemotherapy. Older patients than younger patients

Prone to permanent ovarian failure and menopause, 21 to 25 years of age in patients with ovarian cancer

The risk of failure is increased to about 27 times of children after chemotherapy in patients with premature ovarian failure rate

60% (3). Chemotherapy combined with whole body radiotherapy combined with bone marrow transplantation

To be more obvious, children with 80% faces the risk of premature ovarian failure 4.

Chemotherapy-induced ovarian failure may be reversible at the end

After radiotherapy and chemotherapy can be part of the recovery of ovarian function. At this point, the patient should be pregnant as soon as possible

Rather than delay the birth time, but the time of pregnancy should be at the end of treatment

6 ~ 12 months later, in order to avoid the fetus from the body of the damaged reproductive cells.

2.6 young patients with gynecologic surgery may have ovarian after surgery

Functional failure. For example, after the removal of ovarian cysts in severe endometriosis,

Partial excision of ovarian tissue may result in partial loss of ovarian function, or even failure.

2.7 vascular factors: when the uterus was removed, the uterine artery and vein were removed

The ovarian branch, or the conventional uterine artery embolization, is not a target for the blockage of ovarian blood vessels,

When the ovarian angiogenesis is abnormal, the ovarian blood supply is reduced, and the follicle is degraded.

2.8 social factors due to personal, professional or economic and other social factors delayed childbearing

More and more women are planning. In Holland, the average age at birth is 29.1

At the age of 24.6, nearly 5 years later than the age of 30 years; a child of the age of 34

The number of students increased by 3 times [5]. In the United States, Canada and other countries, has been

Cryopreservation of oocytes to preserve reproductive capacity and establishment of reproductive insurance".

3 protection and preservation of reproductive capacity

3.1 reproductive capacity to protect women with gynecologic surgery for selective protection of the ovaries

Tissue and ovarian function. For example, in the early stage of cervical cancer, malignant degree is low

To protect ovarian function in patients with ovarian ectopic surgery before radiotherapy

Conservative surgery for patients with early epithelial ovarian cancer;

Treatment of early stage endometrial cancer patients with hormone therapy

Can be reduced to a certain extent, radiotherapy or surgery on ovarian function


Recent clinical studies have shown that pretreatment with chemotherapy prior to chemotherapy can reduce chemotherapy

Toxic side effects of drugs on ovarian function. Generally advocated before chemotherapy 7 ~ 10D

Use of gonadotropin releasing hormone agonist (GnRHa) to protect ovarian function

Can. Other hormone replacement therapy, oral contraceptives and inhibitors of apoptosis

1- sphingosine-1-phosphate may also protect ovarian function.

3.2 fertility preservation

The survival rate of 3.2.1 embryos after thawing is 35% ~,

The implantation rate was 8% ~ 30%, and the cumulative pregnancy rate was as high as 60%

18% ~ 20%, is currently the only approved by the North American Society of reproductive medicine

A method to preserve the reproductive capacity of the bed (6).

3.2.2 mature oocytes cryopreservation of frozen oocytes, not only can be used to

The work is preserved in the face of cancer patients with chemotherapy and reproductive capacity, but also become a health

The choice of keeping the reproductive ability of the partners. Vitrification of oocytes

Gradually replace the slow freezing method, may be used to establish the "human egg bank".

3.2.3 immature oocytes (germinal vesicle stage, GV) frozen

GV oocytes loose chromatin, the periphery of nuclear envelope can withstand freezing

Injury (7). However, because of in vitro maturation (in vitro maturation),

IVM system is not perfect, and it is difficult to produce immature oocytes after thawing

Mature oocyte. So far, only 1 cases have been successfully delivered (8).

On the contrary, immature oocytes were cultured in vitro and then cryopreserved by vitrification

The success rate is higher than that of the former, which can be used for the recovery of the natural cycle of cancer patients

Force provides a relatively viable approach (9). The success of oocyte cytoplasm transplantation was found for immature oocytes

The maturation of mature oocyte cytoplasm may be the breakthrough point to improve the -IVM system of immature oocytes (10).

3.2.4 ovarian tissue frozen in 1996, Hovatta et al. (11) for the first time

The feasibility of cryopreservation of ovarian tissue to preserve the function of ovarian tissue

Successful reports of live births have been reported, and it has been proved by transplantation of cryopreserved ovarian group

The feasibility of restoring reproductive ability by weaving (12-17). Cryopreservation of human ovarian tissue is usually performed in two ways

The first is the separation of follicles cultured in vitro or tissue culture in vitro; two

Reproduction, spontaneous pregnancy or assisted reproductive technology.

Human ovarian tissue or follicle in vitro culture system, by the follicular separation method, growth factors, etc.

The effects of different factors on growth and maturation in vitro were not maintained in vitro (18);

However, the success rate of autologous transplantation of human ovarian tissue is very low

There were only 6 reports of a total of 8 cases of live births (12-17) with spontaneous pregnancy or IVF-ET

. However, the study of human ovarian tissue xenotransplantation shows that the heterogeneous body, such as SCID mouse,

The ability to become an intermediate receptor for the recovery of ovarian function, initiate and maintain follicular growth and prolonged development,

Expected to be fertilized

Oocytes [19]. Ovarian tissue transplantation and ovarian function after thawing. egg

The freezing and thawing process of nest tissue damages a large number of follicles

Sufficient to support late transplantation, whether the survival of the transplanted follicle is mature

Potential need to determine the activity of ovarian tissue before transplantation and evaluate the value of transplantation.

In addition, cryopreservation and transplantation of human ovarian tissue are related to medical safety.

Ovarian tissue derived from cancer patients, may carry tumor cells, back to the body

May cause potential risks; if the ovarian tissue is directly exposed to liquid nitrogen

Microbial infection. Therefore, timely and effective detection of tumor cell infiltration and

Microbial infection in order to improve the safety of autologous or allogeneic ovarian transplantation.

Human ovarian tissue was transplanted into SCID mice, which could not only be used to evaluate ovarian tissue

It is also one of the methods of activity and safety

Important way.

3.2.5 ovarian tissue freezing combined with IVM was applied to IVM,

Oocyte vitrification and freezing of ovarian tissue: first remove

Cryopreservation of immature oocytes in ovarian cortex by vitrification, IVM

Ovarian cortex and the success of the flexible use of female fertility preservation

Model of the program [20].

A prospective study on the preservation of reproductive capacity of 3.2.6 female germ cells

It is found that there are female germ cells in the ovary of adult and newborn mice

It was induced to differentiate into follicle (21-22), which may be presumed in human ovarian tissue

The female reproductive stem cells can be induced by inducing the differentiation of female germ cells

It can be used to supplement the ovarian reserve, so that it can not be consumed. however

However, there is no direct evidence for the existence of female reproductive stem

Cellular hypothesis.

4 biological safety of fertility preservation

Embryo freezing, oocyte freezing and ovarian tissue cryopreservation

Progress, from the treatment of infertility to the preservation of reproductive capacity, reproductive energy recovery

The purpose of this study is to evaluate the effects of human oocyte cryopreservation and ovarian tissue cryopreservation

It is still in the experimental stage, and its biological safety needs to be systematic and in-depth


At present, it is known that the toxicity of cryoprotectant and the excessive intervention of in vitro operation

Chemical toxicity and physical damage to oocytes, embryos and ovaries

These short-term effects affect the structure and function of cells at the molecular level

Can result in abnormal genetic material and epigenetic modification. In addition, deep low

Long term effects of temperature preservation, including hardware facilities, storage time, operations management, etc.

Factors may also affect the preservation of reproductive capacity.

The biological safety of reproductive capacity preservation technology is not limited to live births

Growth and genetic characteristics of infants and offspring after birth.

At present, there are few reports in this field. In the preservation of reproductive capacity

A large amount of basic research and clinical follow-up data are needed in clinical application

To prove its long-term safety, to guide and regulate the implementation of the technology of the preservation of reproductive capacity.

5 medical consultation

With the improvement of survival rate, cancer patients are more and more concerned about the reproductive ability

This is not only related to their own quality of life, but also the ability to reproduce, straight

Connected to family harmony. 70% of patients with ovarian cancer have fertility requirements,

29% breast cancer patients hope to restore fertility. Children with cancer

The reproductive status of adults has a decisive influence on their quality of life.

At present, patients and their families have little knowledge of the ability to preserve fertility and even cancer

Specialists also lack knowledge in this area. 34% ~ 72% patients want to know

The treatment of reproductive capacity, the need for guidance, and the current patient access to this

The way of knowledge is very limited. Cancer specialist and reproductive specialist

Reproductive capacity should be saved in consultation and treatment into the patient's treatment plan

Help patients to do a good job of reproductive capacity preservation plan, which requires doctors not only master

The ability to preserve the relevant knowledge, but also to understand the knowledge of religion, law, etc.

Correct and effective guidance. The goal of cancer treatment will not be limited to patients

To improve the quality of life of patients, establish a harmonious family, build

Harmonious society.

To sum up, physiological, iatrogenic and social factors lead to female reproduction

The overall decline in capacity, a variety of techniques to preserve the advantages and disadvantages of female reproductive.

Cryopreservation of embryos is the preferred approach, with high success rate and safety

Exhibition. Secondly, the mature oocytes were cryopreserved, and the oocytes were matured in vitro

The improvement of embryo system, immature oocyte freezing is more than that of mature oocytes

Frozen, better protection of chromosomes and DNA. Ovarian tissue transplantation

Methods the endocrine function and ovulation function of the patient can be recovered

Delivery, is the development trend of fertility preservation. In addition, female born in the ovary

Stem cell research may open up new ways to restore fertility. However, the egg

Cryopreservation of oocytes and ovarian tissue is still in the experimental stage. Human beings

In the improvement of the ability to preserve the reproductive technology, methods, improve the clinical success rate,

Attention must be paid to the long-term safety of various technologies. In addition, through the popularization of health

The ability to preserve knowledge and improve the preservation of non reproductive specialist, patient and family members

Awareness of reproductive capacity, and to carry out medical consultation, will help guide and regulate reproduction

Ability to save effectively and safely.


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