Immunological infertility

　　1. Etiology

　　1. Autoimmune Immunity:Some friends experience immunological infertility due to autoimmune factors. Because of autoimmune factors, such as male sperm and seminal plasma, and female eggs, when they溢出生殖道 and enter other surrounding tissues, it causes immunity, which in turn affects sperm vitality, follicle maturation, and ovulation.

　　2. Allogeneic Immunity:Some cases of immunological infertility are caused by allogeneic immunity. For example, when sperm and seminal plasma act as antigens, antibodies are produced in the female body, leading to sperm agglutination and loss of motility.

　　3. Local Immunity:This is one of the causes of immunological infertility. Generally, local immunity refers to the abnormality of immunoglobulin G, A lymphoid cells in the cervical mucosa and endometrium of women with infertility, leading to female infertility.

　　机体的免疫系统具有保护自身抗原，识别并排斥外来抗原的作用。在正常情况下，由于机体的免疫系统平衡协调作用，不会对身抗原产生免疫损伤；外来抗原能否刺激机体产生有效的免疫应答，取决于入侵抗原的性质、剂量、入侵途径、入侵时机体的免疫状况及有无佐剂等。因此同一抗原刺激不同机体，甚至同一抗原在不同时间刺激同一机体，可产生不同的免疫效果。

　　二、发病机制

　　1、男性抗精子抗体的产生：精子虽为自身抗原，但它于青春期才出现，被自身免疫系统视为“异己”。然而血睾屏障阻碍了精子抗原与机体免疫系统的接触，不会产生抗精子的免疫反应。若血睾屏障发育不完善或遭到破坏，如手术、外伤、炎症等，导致精子外溢或巨噬细胞进入生殖道吞噬消化精子细胞，其精子抗原激活免疫系统，产生抗精子抗体。

　　抗精子抗体产生的另一个可能原因是抑制性T淋巴细胞数量减少或活性下降。此细胞存在于附睾和输精管的皮下组织中。正常情况下，由睾丸网及其输出管漏出的少量精子抗原可激活抑制性T细胞，使成熟B细胞识别抗原的过程变得迟钝，降低了机体对精子抗原的体液免疫反应，形成免疫耐受。当抑制性T细胞数量或活性下降以及精液内补充抑制性T细胞的因子缺乏时，可产生抗精子抗体。

　　2、女性抗精子抗体的产生：正常精液中含有前列腺素E和一种糖蛋白，具有免疫抑制作用，精液沉淀素具有抗补体活性。这些免疫抑制因素在正常情况下可抑制女方免疫活性细胞针对精子抗原的免疫应答，诱导免疫耐受。若丈夫精液中免疫抑制因子的缺乏可导致女方产生抗精子抗体。夫妻双方的生殖道感染可致女方抗精子抗体的产生，可能是由于感染使局部的非特异性免疫反应加强引起的。临床研究表明，男方精液中白细胞增加与女方生殖道局部和血清中抗精子抗体的发生明显相关，提示感染因子作为天然佐剂，免疫相关细胞与精子抗原共同介入女性生殖道，产生同种抗精子免疫。

　　在生殖道粘膜破损的情况下性交，可使精子抗原通过破损的粘膜上皮屏障，进入上皮下的T淋巴细胞，产生抗精子抗体。异性间的肛交或口交是女性产生抗精子抗体的原因之一。另外，某些助孕技术如直接腹腔内人工授精，可导致大量精子进入腹腔，被腹腔中的巨噬细胞吞噬后，将精子抗原传递至盆腔淋巴结内的辅助性T淋巴细胞，从而诱发抗精子的免疫反应，使血清中出现暂时的抗精子抗体升高。

　　3、抗精子抗体干扰生育的环节

　　（1）抗精子头部的抗体可干扰精子获能及头粒反应。

　　（2）细胞毒抗体在补体参与下使精子细胞膜损伤，精子死亡，抗精子尾干的抗体抑制精子活动。

　　（3）抗精子抗体的Fc段与宫颈粘液糖蛋白结合，干扰精子穿过排卵期宫颈粘液。

　　（4）抗精子抗体的调理作用增强生殖道局部吞噬细胞对精子的吞噬作用。

　　（5）抗精子头部的抗体能阻止精子与透明带及卵细胞膜结合，抑制受精。

　　1、阻止精子穿过宫颈黏液：抗精子抗体可使精子凝集成团块，阻碍精子活动。精子制动抗体具有细胞毒反应，致精子死亡或影响精子活动。此外，可能对精子代谢和精子收缩蛋白功能也有一定的影响。

　　2、影响精子酶的活动：抑制透明带和放射冠的分散作用，包括：

　　（1）顶体蛋白酶：能促进精子穿过透明带和促进精卵融合。

　　（2）精子透明质酸酶：能使卵丘（放射冠）分散。精子抗体主要是抑制透明质酸酶的活力而干扰精子的分散作用。

　　3、影响胚胎发育：造成免疫不育的原因有很多种，如感染、双侧生殖道阻塞、睾丸外损伤（扭伤）、睾丸活检后、隐睾、精索静脉曲张、同性恋（肛交）等，特别要询问有无输精管结扎病史。凡能引起睾丸血睾屏障破坏、附属性腺感染、睾丸受高温影响或损伤等原因而导致精子抗体形成，都可引起免疫性不育。

　　4、封闭顶体膜上的透明带识别点，抑制精子对透明带的附着与穿透作用。

　　1、抗体引起精子凝集作用，进而降低精于活动力，造成女性不孕症。

　　2、影响精子膜上颗粒运动，进而干扰精子获能；同时，影响精子顶体酶的释放，进而导致女性不孕。

　　3、会干扰精子粘附到卵泡透明带上，进而影响受精，导致女性不孕症。

　　4、抗体与精子粘合后活化补体、和抗体依赖性细胞毒活性，加重局部的炎症反应。

　　1、女性朋友们想要良好的预防免疫性不孕首先应该防止卵巢出现早衰现象。在日常生活中，女性要坚持喝牛奶，多吃鱼、虾等高钙食物，坚持锻炼身体，提高机体免疫力，做好孕育准备。

　　2、避免衣原体的感染也是女性朋友们预防免疫性不孕需要注意的问题。

　　3、避免作息混乱，只有维持良好的生活作息，才可维持女性机体正常排卵功能。否则将导致女性不排卵，继而出现不孕现象。

　　4. Over-frequent sexual intercourse or chaotic sexual life will cause sperm antibodies in women. Once sperm antibodies appear, women will find it difficult to become pregnant again. Therefore, avoiding over-frequent sexual intercourse and chaotic sexual life is also one of the methods to prevent immunological infertility.

　　5. Whether in public places or at home, women should quit smoking and reduce exposure to second-hand smoke.

　　5. Poor mental and emotional health can not only induce various diseases but also lead to female infertility. Therefore, avoiding mental stress and regulating self-emotions in daily life is one of the main methods for women to prevent immunological infertility.

　　I. Examination of female immunological infertility

　　1. Cervical mucus contact test

　　The examination of cervical mucus is mainly to check whether there are anti-sperm antibodies in the cervical mucus. If it is performed during the ovulatory period, the commonly used method is to use a glass slide to place the semen and mucus on the glass slide, and then place it in the microscope for examination.

　　2. Cervical mucus examination

　　The examination of female immunological infertility projects can usually be detected by the condition of cervical mucus, which is mainly after sexual life between couples. It can be seen through the survival rate of cervical mucus and sperm to detect the penetration rate of sperm. If the penetration rate of sperm does not meet the standard, it is due to the existence of certain immune antibodies inside.

　　3. Ovarian-pituitary function examination

　　Basal body temperature measurement (BBT): Place the thermometer under the tongue for 5 minutes every morning in a resting state and record the temperature in a special table. The normal basal body temperature of women shows a biphasic pattern under the influence of ovarian function. It can understand the date of ovulation, whether there is an ovulation date, and whether there is an ovulatory dysfunction.

　　4. Immunological examination of reproductive products

　　Immunological examination, this examination mainly includes the examination of sperm antigens in the body, the examination of anti-sperm antibodies, and the examination of anti-endometrial antibodies. These targeted examinations can be further carried out for immunological examinations of body fluids.

　　5. Tubal patency test

　　The examination methods include hysterosalpingography, hydrotubation, and ventilation test of fallopian tubes, to understand whether the fallopian tubes are patent. 

　　6. Endometrial pathological examination

　　A method to understand the ovulatory or luteal function status. At the same time, it can also understand the size of the uterine cavity, and internal and external uterine cavity lesions such as tuberculosis, fibroids, etc.

　　7. Immunological examination

　　Immunological examination can detect AsAb in the blood, antibodies that can cause sperm agglutination or loss of activity and cause infertility.

　　8. Cervical mucus examination

　　Understand the situation of ovulation and luteal function.

　　II. Examination items for male immunological infertility

　　1. Medical history examination

　　The patient's medical history must be checked clearly, such as whether there are any problems with the patient's inheritance, whether there has been a history of cryptorchidism, orchitis, or orchitis caused by mumps, whether cottonseed oil is often consumed, tight pants are worn, and so on. Through the medical history, we can find some problems.

　　2. General physical examination

　　Conduct a detailed physical examination, checking the size, hardness, and elasticity of the testicles, the patency of the seminal vesicles, and the normal function of the prostate and seminal vesicles.

　　3. Immunological factor examination

　　Immunological factors also need to be tested. If no obvious problems are found in these tests, it may be that some prostatitis or damage factors have occurred, and at this time, we need to check for the presence of immunological factors.

　　Malnutrition can affect the ovulation cycle in women and the sperm quality in men. Women are best to keep their weight within a standard range of ±10%. On the other hand, high-fat foods can cause weight gain, also leading to menstrual irregularities and poor ovulation. In addition, the intake of caffeine can reduce the chances of conception.

　　Excessive beta-carotene can affect the synthesis of lutein in the ovary, leading to a decrease in secretion, and some may even cause amenorrhea, anovulation, and irregular menstruation. If a large amount of carrots is consumed, it can cause an excessive level of beta-carotene in the blood, leading to infertility, amenorrhea, anovulation, and other abnormal phenomena.

　　For creating a suitable environment for sperm by changing the acid-base balance in the human body through diet, one can eat some acidic foods or foods rich in calcium and magnesium. For example, unsalted dairy products, beef, eggs, milk, peanuts, walnuts, almonds, grains, and aquatic products. Alkaline foods rich in potassium and sodium include: soda crackers, cream-free pastries, various juices, root crops in grains such as sweet potatoes, potatoes, fruits, chestnuts, etc.

　　Food additives can also cause infertility. Many studies in Western countries have confirmed that food additives such as monosodium glutamate can affect the normal function of male sperm. Moreover, monosodium glutamate has a tendency to accumulate in the human body. 'Phthalates' can also cause a decrease in the number of male sperm and affect the ovarian function of women, thereby affecting women's fertility.

　　1. General treatment

　　1. Isolation therapy:After using a condom for 3 to 6 months, women with immunological infertility can avoid further stimulation of sperm antigens by the male partner. After the antibody titer disappears, sexual intercourse during the ovulation period can be expected to achieve pregnancy.

　　2. Immunosuppressive therapy:Adrenal cortical hormone drugs can be used to treat immune infertility, such as the application of prednisone 5mg three times a day two weeks before ovulation. There are also reports of the local application of hydrocortisone in the vagina to treat infertility in women with anti-sperm antibodies in cervical mucus. The reported pregnancy rate is between 20% and 45%.

　　3. Artificial insemination in the uterine cavity:When sperm antibodies in cervical mucus interfere with pregnancy, the husband's semen can be processed in vitro, separating high-quality sperm for artificial insemination in the uterine cavity.

　　4. In vitro fertilization and embryo transfer (IVF):If there is a persistent high titer of anti-sperm antibodies in a woman's body, it is an indication for in vitro fertilization and embryo transfer (IVF). Some reports have shown that for immune infertility, the technique of in vitro fertilization and embryo transfer can achieve a fertilization rate of 83% and a pregnancy rate of 33%.

　　5. Gamete Intrafallopian Transfer (GIFT):Nerwe et al. reported on 16 male patients diagnosed with immune infertility and their spouses undergoing GIFT, among whom 7 couples (43%) became pregnant, thereby considering it a very effective and safe method.

　　II. Male Infertility

　　For infertility caused by high concentrations of sperm antibodies in the body due to male autoimmune disease, the following methods can be tried for treatment:

　　1. Immunosuppressive Treatment:Use adrenal cortical hormones, treat with low doses for a long time according to specific conditions, or use high-dose shock therapy, and have sex when the level of sperm antibodies in the body decreases to a certain extent, to increase the chance of conception.

　　2. Collecting Semen:Then, use a special sperm washing solution to wash off the antibodies attached to the sperm surface and perform artificial insemination.

　　3. Using Testosterone Rebound Therapy:According to the physiological characteristics of testosterone, a large dose of testosterone is used first to inhibit the spermatogenic epithelium, and then testosterone is discontinued, so that more sperm are produced after the spermatogenic epithelium is released from inhibition. This is the testosterone rebound therapy. When the number of sperm decreases, the antibody titer also decreases or disappears. Having sex during the period when the sperm count rebounds and the antibody level has not increased significantly can increase the chance of conception.

　　4. Consider Autoimmunity:It is caused by inflammation such as orchitis and epididymitis, and primary diseases need to be treated actively at the same time.

　　III. Female Infertility

　　For immunological infertility caused by antibodies in the female body, the method of condom sex or simultaneous administration of corticosteroid immunosuppressants can be tried for treatment.

　　1. Avoiding Antigen Contact:Using a condom during each sexual intercourse can avoid further stimulation of the female by sperm antigens. When the level of sperm antibodies in the female decreases, encourage patients to have condomless sex during the ovulation period or undergo artificial insemination.

　　2. Immunosuppressive Methods:Adrenal cortical hormone drugs have anti-inflammatory and macrophage toxic effects. Therefore, they can be used to treat immunological infertility.

　　3. Intrauterine Insemination:When sperm antibodies interfere with fertility in the cervical mucus of the patient, the husband's semen can be processed in vitro, and high-quality sperm can be separated for artificial insemination. This method avoids the restrictive effect of sperm antibodies in cervical mucus on sperm passage.

　　4. In Vitro Fertilization:Sperm and egg are fertilized in vitro, and implanted into the uterine cavity 3-5 days after fertilization, so sperm do not need to have local contact with the female reproductive tract containing sperm antibodies before fertilization. After fertilization, due to the protective effect of the zona pellucida of the embryo, sperm antibodies cannot attack the embryo, and then the embryo implants.