Idiopathic infertility, also known as unexplained infertility, is a type of infertility in which the cause of infertility cannot be identified by applying the available diagnostic tools. According to the staging analysis of a group of 2389 cases (1996) of male infertility, among which semen abnormalities accounted for 10%, testicular failure accounted for 9%, obstructive accounted for 6%, cryptorchidism accounted for 6%, varicocele accounted for 7%, others accounted for 7%, and idiopathic accounted for 25%. There are also reports of idiopathic accounting for 60% of the cases. It can be seen that the level of diagnosis varies greatly from unit to unit and from individual to individual. In fact, this proportion is constantly changing with the progress of science and technology, and the proportion of idiopathic infertility will certainly become lower and lower as time goes by. On the other hand, hospitals at all levels have different equipment conditions and doctors at all levels have different skill levels to arrive at a diagnosis of etiology, so it is difficult to make an accepted diagnostic step of idiopathic infertility with certainty. However, if we can carefully consider and analyze more in the routine diagnosis, and add or improve the equipment and technology as much as possible, we can certainly make the proportion of idiopathic infertility greatly reduced. The problems that should be noted in the diagnosis are discussed item by item: I. Find the cause from the medical history Medical history often reflects some of the triggering factors of infertility, ignoring the detailed understanding of the medical history, it is easy to lose some important clues, resulting in unknown causes. For example: 1. Sexual history The frequency of sexual intercourse is proportional to the time required to obtain a pregnancy. Sexual dysfunction such as erectile dysfunction (impotence), premature ejaculation (ejaculation occurs before vaginal insertion), non-ejaculation or retrograde ejaculation can be the cause of infertility; 2. Occupational history Such as high temperature operators, long distance drivers, history of radiation exposure and chemical drug exposure may affect the quality of semen and cause infertility; 3. Disease history Mumps orchitis, tuberculosis, typhoid, influenza, syphilis, and other diseases. The history of many drugs can inhibit the occurrence and discharge of sperm, such as the antineoplastic drugs cyclophosphamide, vincristine, salicylic acid azo sulfadiazine pyrimethamine, anserine, insulin and colchicine, etc. The reason for this is that many doctors simply ask for a medical history or prescribe medication to patients based on semen tests without doing physical examination, which is absolutely wrong. Physical examination can provide important clues to the cause of the disease, so it should be careful and comprehensive, not to miss every detail that may provide the cause of the disease, focusing on: (1) secondary sexual characteristics; (2) penis; (3) testes; (4) epididymis; (5) vas deferens; (6) varicocele. Third, find the cause from semen analysis. Semen analysis not only provides the true state of spermogenesis function in the testes, but also reflects the situation at the beginning of the spermatogenic cycle 3 months ago, and can also understand the function of the epididymis and accessory gonads, so it should be carefully analyzed. However, the semen analysis done in many primary care hospitals is too crude and simple to make analytical judgments. In order to reduce the proportion of idiopathic infertility, semen analysis must be careful and detailed, and each item should be studied and, if necessary, combined with other tests to clarify the cause. Fourth, from the sperm function to find the cause There are many patients whose semen routine analysis is normal and the female examination is also normal, then it should be checked whether their sperm function is normal? At present, the sperm function tests that can be done are: (1) sperm-cervical mucus interaction test; (2) sperm membrane integrity; (3) evaluation of the Xiangxiu reaction; (4) evaluation of sperm-egg interaction. V. Immunological aspects to find the cause World Health Organization in 1988 reported 6407 cases of male infertility diagnosed by the examination of 2, 9% of patients with immune factors, of which, immune infertility in primary infertility accounted for 2, 7%, while secondary infertility in immune factors accounted for 4, 0%. Therefore, anti-sperm antibodies should be investigated in patients with unexplained infertility and the following conditions: (1) history of urogenital tract injury and infection; (2) abnormal semen analysis: sperm density <20×10/ml, viability <20%, normal form <70%, sperm agglutination, delayed semen liquefaction; (3) azoospermia with non-seminogenic disorders; (4) poor post-coital test; (5) sperm penetration to the zona pellucida abnormal hamster egg test. Sixth, from the biochemical analysis of seminal plasma to find the cause Semen consists of two parts: sperm and seminal plasma. Seminal plasma is a mixture of secretions from some accessory sex glands such as epididymis, seminal vesicles, prostate gland, urethral bulb gland and paraurethral gland. They each have their own representative substances. Therefore, it is possible to understand the function of each organ by measuring the signature substances in seminal plasma separately. 1. Fructose Fructose in seminal plasma is secreted by the seminal vesicles. Therefore, the determination of fructose content can initially measure the function of seminal vesicles; 2, acid phosphatase and citric acid Acid phosphatase and citric acid in seminal plasma are special secretions of the prostate, and the determination of their content can determine the function of the prostate; 3, carnosine The carnosine in seminal plasma mainly comes from the epididymis and seminal vesicles, and the observation of the amount of carnosine in seminal fluid can help evaluate the function of the epididymis and seminal vesicles, but at present, it is mostly used clinically to understand the function of the epididymis. If the determination of carnitine in seminal plasma is combined with the determination of fructose, it is of some value to clinically evaluate the function of epididymis and seminal vesicles as well as to determine the site of obstruction, etc.; 4. Glycosidase in epididymis, the activity of glycosidase is high, so the determination of ˉglycosidase activity in seminal plasma is an indicator to test the function of epididymis. The hormones related to male reproductive activity come from the hypothalamus, pituitary gland and testes. The methods of measurement can be divided into static measurement and excitation test. The former measures blood levels of follicular spontaneous hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T), and estradiol (F2) to determine the cause of infertility. The latter provides further insight into the site of endocrine abnormality. VIII. Finding the cause from testicular biopsy Testicular biopsy can directly estimate the function of spermatogenesis and the degree of sperm disorder, the ability of testicular synthesis of androgens and the cause of their disorder. Therefore, testicular biopsy can not only provide direct information for the diagnosis of male infertility, but also provide a lot of useful information and basis for the selection of treatment measures and the prognosis. Although testicular biopsy has been re-recognized and re-evaluated in recent years, and advances in hormone determination and chromosomal analysis have reduced the indications for certain biopsies, it is still a valuable diagnostic method due to the direct histological display. The reason for this is that vasectomy is not a routine test in the diagnosis of male infertility, but in some cases it can play a decisive role in determining the diagnosis. Although vas deferens hypoplasia also causes obstruction of the vas deferens, it is not necessary to use imaging to diagnose it. Bead-like changes of the vas deferens are the pathology of tuberculosis, and the angiogram reveals enlarged lumen with irregular margins and dilated areas. Calcification of the vas deferens and seminal vesicles is seen in the elderly, especially in those with diabetes mellitus, and also in the elderly with vas deferens infection. Ten, from cytogenetics to find the cause According to statistics, cytogenetic abnormalities account for about 10% to 25% of the causes of male infertility. Some people are in good health, but due to chromosomal or genetic abnormalities that affect the gonads lead to infertility, these people can get married and have a normal sex life but can not have children. Therefore, chromosomal examination should be done for idiopathic infertility. Chromosomal aberrations that can cause infertility can be divided into two categories: numerical aberrations and structural aberrations. If there are more or less than 46 chromosomes, they are considered as numerical aberrations. 2, structural aberrations Structural aberrations are the result of chromosomes broken and then glued together under the action of repair enzymes. It is of great importance to male infertility and habitual abortion of spouse. All kinds of aberrations can affect the normal spermatogenesis process and cause infertility. The incidence of structural aberrations is higher in azoospermia and oligospermia. Molecular biology has confirmed the existence of a gene related to spermatogenesis on the long arm of the Y chromosome, whose deletion will lead to azoospermia or severe oligospermia in patients, hence the name Azoospemia factor (AZF). Therefore, testing for AZF in patients with azoospermia or severe oligospermia can lead to a definite cause of these "unknown" cases. To realize the desire for fertility, sperm must have effective motility (tail), intact acrosome and nucleus, and well connected segments. However, the integrity and function of these structures are difficult to measure by semen analysis with an ordinary microscope. Therefore, the use of transmission electron microscopy to observe sperm in semen can reveal many abnormalities in subcellular structures and thus elucidate the true cause of infertility. What are the conditions that require electron microscopy of semen? Although there are too many variations in infertility to make a definitive indication, the following should be considered: (1) repeated semen examinations showing normal density, normal motility and "normal" morphology, but prolonged infertility and/or negative hamster egg penetration test; (2) inactive or abnormal sperm activity with "normal" morphology (2) sperm inactivity or abnormal activity with "normal" morphology, to distinguish whether it is really dead sperm or motility disorder due to defective tail ultrastructure; (3) sperm generally lacking normal head shape and size as seen in semen analysis, such as round head to exclude undeveloped acrosome and small head to exclude dysplastic acrosome or severed head; (4) semen examination remains unchanged after several months or years, or (5) When the couple wants to know the exact cause of the poor semen quality. The clinical trial treatment, and repeated semen examinations or further examinations may be terminated after abnormalities are detected by electron microscopy, and the patient is advised to choose other treatments.