|Year : 2020 | Volume
| Issue : 1 | Page : 11-17
Diagnostic guidelines for infertility
Zi-Jiang Chen1, Jia-Yin Liu2, He-Feng Huang3, Jie Qiao4, Can-Quan Zhou5, Guo-Ning Huang6, Ying-Pu Sun7, Dong-Zi Yang8, Xiao-Yan Liang9, Qi Yu10, Yun Sun11, Zheng Li11, Li-Qing Fan12, Cong-Jian Xu13, Yuan-Hua Huang14, Xue-Hong Zhang15, Jing Yang16, Shao-Ming Lu1, Lin-Lin Cui1, Jun-Hao Yan1, Jin-Fang Lin13
1 Center for Reproductive Medicine, Shandong University, Jinan 250000, China
2 Clinical Center for Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 211129, China
3 Department of Reproductive Medicine, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
4 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
6 Chongqing City Institute of Reproduction and Genetics, Chongqing 400010, China
7 Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China
8 Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
9 Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China
10 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
11 Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
12 Sperm Bank of Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha 410008, China
13 Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
14 Reproductive Medicine Center, The First Affiliated Hospital of Hainan Medical University, Haikou 570120, China
15 Department of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
16 Center for Reproductive Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
|Date of Submission||30-Nov-2019|
|Date of Decision||20-Feb-2020|
|Date of Acceptance||27-Feb-2020|
|Date of Web Publication||2-Apr-2020|
School of Medicine, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai 200030
Clinical Center for Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 211166, China Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 201129
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191
Center for Reproductive Medicine, Shandong University, No. 157 Jingliu Road, Jinan 250000
Source of Support: None, Conflict of Interest: None
Infertility seriously endangers the reproductive health of women at childbearing age. It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse. Broadly defined, infertility includes two aspects – failure to conceive or have a live birth. This guideline only addressed content relevant to the former. It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, based on relevant guidelines of the World Health Organization, the American Society for Reproductive Medicine, the National Institute for Health and Clinical Excellence, as well as the clinical practice in China. The guideline was reviewed by experts and doctors from medical institutions at all levels, which is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide.
Keywords: Diagnostic Guidelines, Etiological Classification, Infertility Evaluation
|How to cite this article:|
Chen ZJ, Liu JY, Huang HF, Qiao J, Zhou CQ, Huang GN, Sun YP, Yang DZ, Liang XY, Yu Q, Sun Y, Li Z, Fan LQ, Xu CJ, Huang YH, Zhang XH, Yang J, Lu SM, Cui LL, Yan JH, Lin JF. Diagnostic guidelines for infertility. Reprod Dev Med 2020;4:11-7
|How to cite this URL:|
Chen ZJ, Liu JY, Huang HF, Qiao J, Zhou CQ, Huang GN, Sun YP, Yang DZ, Liang XY, Yu Q, Sun Y, Li Z, Fan LQ, Xu CJ, Huang YH, Zhang XH, Yang J, Lu SM, Cui LL, Yan JH, Lin JF. Diagnostic guidelines for infertility. Reprod Dev Med [serial online] 2020 [cited 2021 Jan 17];4:11-7. Available from: https://www.repdevmed.org/text.asp?2020/4/1/11/281853
| Introduction|| |
Infertility is a status of subfertility, which refers to the failure to get successful pregnancy after 1 year or more of regular unprotected intercourse. Clinical pregnancy refers to the presence of clinical signs of pregnancy and one or more gestational sacs confirmed by ultrasound scan. Abnormal clinical pregnancy includes ectopic pregnancy (including cervical pregnancy and cesarean scar pregnancy), early pregnancy loss, abortion, stillbirth, premature delivery, and prolonged pregnancy, but not includes biochemical pregnancy (preclinical spontaneous abortion/miscarriage).
Broadly defined, infertility comprises two aspects – failure to conceive or have a live birth. This guideline only addressed the content refer to the former. It was drafted by the endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, and was reviewed by more than 90 doctors within this area from medical institution all over the country. It is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide. For the diagnosis of single disease involved in this guideline, please refer to the corresponding diagnostic criteria, for example, the diagnosis of polycystic ovary syndrome (PCOS).
| Classification of the Etiology|| |
According to the pregnancy history of the female partner, infertility can be divided into primary infertility (without previous pregnancy) and secondary infertility (with previous clinical pregnancy). Etiologically, the disease can also be divided as female infertility, male infertility, and unexplained infertility.
The causes of female infertility mainly include ovulatory dysfunction and pelvic factors that affect the generation, development, discharge, transport, and fertilization of the oocyte, or early embryo development and implantation.
Common causes of ovulatory dysfunction include the following:
- Hypothalamic amenorrhea or menstrual disorders, including (1) amenorrhea caused by anorexia nervosa; (2) excessive obesity or emaciation, excessive exercise; (3) idiopathic hypogonadotropic amenorrhea; (4) Kallmann syndrome, drug factors, etc
- Pituitary amenorrhea or menstrual disorder, including idiopathic hyperprolactinemia, pituitary adenoma, Sheehan's syndrome, and empty sella syndrome
- Ovarian amenorrhea or menstrual disorders, including (1) premature ovarian insufficiency caused by genetic factors, autoimmune diseases, or iatrogenic factors; (2) PCOS characterized by oligo-ovulation, oligomenorrhea, clinical and/or biochemical hyperandrogenemia, and metabolic dysfunction; (3) Turner syndrome (karyotype 45, X) and other chimeric chromosomal abnormalities; (4) congenital gonadal hypoplasia; (5) functional ovarian tumor including abnormal androgen or estrogen secreting tumor
- Other endocrine diseases, such as congenital adrenal hyperplasia, Cushing's syndrome, adrenocortical hypofunction, and hypothyroidism.
- Congenital malformation of the reproductive system, such as Müllerian duct aplasia
- Cervical factors, such as cervical insufficiency and other cervical diseases
- Uterine disorders, such as endometrial lesions, uterine tumors, and intrauterine adhesions
- Oviduct and its surrounding disorders, such as oviduct obstruction, peritubal adhesions, hydrosalpinx, and pelvic adhesion
Male infertility is mainly caused by male sexual dysfunction and/or semen abnormalities, such as azoospermia, oligoasthenozoospermia, teratozoospermia, and seminal plasma abnormalities.
Azoospermia is the absence of spermatozoa in the sediments of semen after 2–3 times of high-speed centrifugation. It mainly includes primary azoospermia (azoospermia with spermatogenic dysfunction) and obstructive azoospermia.
Oligoasthenozoospermia is defined as when the number and/or motility of sperm is less than the lower reference limits in at least 2 tests of standard semen analysis. It can be further divided into oligozoospermia, asthenozoospermia, oligoasthenozoospermia, and cryptozoospermia. Cryptozoospermia refers to the presence of isolated spermatozoa that can be only detected after centrifugation but not in routine semen analysis.
Teratozoospermia refers to the condition that the percentages of the normal form spermatozoa below the lower reference limit. Modified pasteurization method is recommended for sperm morphology staining.
Seminal plasma abnormality
Sometimes, the semen test shows normal concentration, motility, total count, and morphology of the sperms, but the physical properties, biochemical properties, and bacterial contents in seminal plasma are abnormal. Most cases are idiopathic and have not been completely proved to contribute to infertility.
The causes of semen abnormality include congenital abnormality, systemic factors, reproductive system diseases, and others.
- Congenital abnormality mainly refers to congenitally developmental malformation and genetic diseases. The former involves cryptorchid testes or incomplete testicular descent, congenital absence of seminal vesicle or spermaduct, congenital testicular dysplasia, and hypergonadotropic hypogonadism. The latter mainly includes karyotype abnormality, Y chromosome microdeletion, Klinefelter syndrome and its chimerism, Sertoli cell-only syndrome, androgen receptor gene mutation, and immotile cilia syndrome
- Systemic factors include endocrine abnormalities associated with several diseases such as idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, and hyperprolactinemia. Immunogenic infertility has no definite diagnostic criteria. Other possible causes include smoking, excessive alcohol consumption, drug abuse, environmental factors, and recent high fever
- Reproductive system diseases mainly include (1) dysfunction of intercourse and/or ejaculation, such as erectile dysfunction, insufficient intercourse frequency, nonejaculation, and retrograde ejaculation caused by organic and/or psychological factors; (2) secondary testicular injury or iatrogenic injury; (3) varicocele with abnormal semen parameters; and (4) male accessory gonad infection including epididymitis, prostatitis, and seminal vesiculitis.
Unexplained infertility is a status of subfertility. The possible causes include potential uterine and/or Fallopian tube More Details factors, possible oocyte or sperm abnormalities, fertilization failure, embryo development arrest, repeated embryo implantation failure, and immune factors. However, it cannot be identified by current examinations.
| Evaluation|| |
Various causes of infertility may coexist. The diagnosis should be based on the careful evaluation of medical history, physical examination, and auxiliary examination results.
Medical history collection
Information about menstruation and related influencing factors, marriage and childbearing histories, and high-risk factors that may affect fallopian tube or pelvic environment should be carefully asked in order to get indications about the possibility of ovulatory dysfunction or abnormal pelvic factors [Table S1].
Physical examinations include general and gynecological examinations as following:
- General examination mainly refers to the development and nutritional status such as height, weight, body fat distribution, olfactory function, secondary sex characteristics, thyromegaly, and skin changes
- Bimanual examination and/or vagino–recto–abdominal examination should be performed to confirm the following items: vulvar development, pubic hair distribution, clitoris size, and the presence of abnormal vaginal secretion; whether the cervix is smooth without abnormal secretion; position, size, shape, texture, and mobility of the uterus; whether the accessory area is thickening, with mass, or tenderness; whether the rectouterine pouch and uterosacral ligament have nodules or tenderness; and whether the lower abdomen has mass, tenderness, or rebound tenderness.
Specific auxiliary examination should be selected according to the patients' medical history and positive physical examination results, such as pelvic ultrasound, hormone test, and fallopian tube test.
1. Pelvic ultrasound examination should be used as a routine for female patients with infertility, and transvaginal ultrasound is recommended. The following items should be involved:
(1) The position, size, and shape of the uterus, myometrium structure, endometrial thickness, and classification
Recommendations: (1) Abnormalities of uterine morphology indicates uterine malformation. (2) Mass in uterine wall indicates myoma or endometrioma. Size and the relationship of the mass with the uterine cavity, especially whether the endometrium line is changed or not should be noticed. Three-dimensional (3D) ultrasound, magnetic resonance imaging (MRI), or hysteroscopy should be considered when necessary. (3) Abnormal morphology or mass in endometrium indicates intrauterine adhesion, endometrial scarring, endometrial polyps, or submucous uterine myoma. Normally, the endometrium thickens gradually with follicle development, reaching a thickness of about 9 mm in the late follicle phase. The “three-line sign” of the endometrium is clear in the follicular phase (Type A). During the ovulation phase, the endometrial echogenicity increased and the sign of “three lines” is vague (Type B). In the luteal phase, the endometrium is a hyperechoic mass without “three lines” (Type C)
(2) Evaluation of the ovaries including the ovarian volume, the count of the antral follicles with diameter between 2 and 9 mm, the size of the dominant follicle, and the presence of any abnormal mass in the ovary. If there is any abnormal mass, then the size, characteristics, and relationship with adjacent organs should be reported as well
Recommendations: (1) Normally, the antral follicle count should be >9 in total of both ovaries and <12 within one ovary. (2) Either of the ovary with >12 antral follicles indicates a sign of polycystic ovary.(3) Having less than 5–7 antral follicles in both the ovaries is a sign of ovarian insufficiency, which requires reexamination and confirmed based other indicators. (4) The cyst with sand-like echogenicity indicates the possibility of endometrial cysts in the ovary. Persistent or continuously enlarging cystic or solid mass indicates the presence of ovarian tumor. Mass occurred secondary to ovulation induction needs to be distinguished from physical follicular cyst or corpus luteum
(3) Ovulation monitoring for follicular development, ovulation, as well as the dynamic change of the endometrium meanwhile
(4) The presence of abnormal echogenicity around the ovary as well as its characteristics, shape, and size.
Recommendations: (1) Sausage-shaped or beaded irregular anechoic area with incomplete hyperechoic band inside indicates the presence of hydrosalpinx. (2) Encapsulated or nonencapsulated fluid in pelvic cavity indicates pelvic adhesion. Mesosalpinx cyst and paraovarian cyst, as well as pelvic or tubal abscess, should be distinguished
2. Hormone tests include serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol (E2), testosterone, progesterone, and thyroid stimulating hormone. Each parameter showed different clinical indications.
(1) Basal FSH level is an indicator of ovarian reserve. It is important to distinguish between the followings: (1) decreased ovarian function: >12 U/L; (2) ovarian insufficiency: ≥25 U/L; (3) ovarian failure: ≥40 U/L; and (4) lower limit of normal range: 5 U/L
(2) Basal LH level increases gradually as the ovarian function decreases; LH/FSH ratio ≥2 indicates the possibility of PCOS
(3) Basal E2 level is often less than 292.8 pmol/L (80 pg/mL). Its increase suggests decreased ovarian function. During follicular phase, E2 level will elevate with the follicle development. Each mature follicle can secrete about 1,098 pmol/L (300 pg/mL) of E2
(4) Low basal levels of FSH, LH, and E2 indicate hypogonadotropic ovulatory dysfunction. Elevated FSH and LH levels with reduced E2 level indicate hypergonadotropic ovulatory dysfunction or decreased ovarian function
(5) If the prolactin level increases, the women should have a retest with the impact factors excluded. Computed tomography (CT) or MRI examination should be considered to confirm the presence of pituitary adenoma if necessary. Hyperprolactinemia accompanied by irregular menstrual cycle, amenorrhea, anovulation, or luteal-phase deficiency can be considered as the cause of infertility
(6) If the level of testosterone exceeds the higher limit of normal range by 2.0–2.5 times, an androgen-secreting tumor in the ovary or adrenal gland will be indicated
(7) Normal ovulation is suggested with the progesterone (P) level in luteal phase above 9.51 nmol/L (3 ng/mL). The P level of the middle luteal phase is an indicator of luteal function, which is mostly above 31.7 nmol/L (10 ng/mL). However, it is difficult to determine the exact threshold
(8). A sharp increase in the urinary LH level in the middle of the menstrual cycle indicates the ovulation, which can be dynamically monitored. The ovulation mostly occurs 1–2 days after the peak of urinary LH
Except for the above classical endocrine parameters, anti-Müllerian hormone (AMH) is being widely applied to evaluate ovarian reserves. Its level is relatively stable across the menstrual cycle and strongly correlates with the basal antral follicle count. However, due to the significant individual differences, no consensus has been made regarding the diagnostic cutoff value or reference range. Besides, it should be noticed that exogenous hormone usage (such as oral contraceptives and gonadotropin releasing hormones), obesity, and hypogonadotropic hypogonadism may affect the result of the AMH test
3. For the examination of fallopian tube, hysterosalpingography (HSG) is recommended as the first-line screening method. 3D real-time ultrasound HSG can also be used for the evaluation under certain conditions. HSG should be performed 3–7 days after the vaginal bleeding has end. Before the examination, the couple should avoid intercourse and inflammation in the reproductive system. During the examination, the uterine cavity shape, the track, shape, and position of the fallopian tube, and the distribution of the contrast medium in the pelvic cavity should be observed. HSG can indicate uterine cavity abnormalities such as intrauterine adhesion, intrauterine neoplasm, and uterine malformation. If the fallopian tube track is rigid, disappeared partly or totally, or with contrast medium accumulation locally, it should be suggested that the tubal patency is affected or even obstructed. If the contrast medium accumulates in the enlargement terminal part of the tube, hydrosalpinx should be considered. It is noteworthy that HSG is an invasive procedure. Thus, it is not the first-line recommendation for the evaluation of infertility. It is only suggested for the patients that cannot be diagnosed in etiology after semen analysis, gynecological examination, ovulation monitoring or therapeutic diagnosis, or plan to perform artificial insemination.
- Basal body temperature measurement can be used as a preliminary self-evaluation method for young infertile female patients with irregular cycle. It can be a supplementary method to other ovulation monitoring methods, but cannot be taken as the only support evidence
- Laparoscopy or hysteroscopy: Laparoscopy is not a routine examination. It is mainly applicable to patients with positive signs but cannot be diagnosed through imaging examination, or those with other indications for laparoscopy, or those needed to confirm the diagnosis of unexplained infertility. Hysteroscopy is either not a routine examination, but could be used in patients with suspected abnormal uterine cavity according to the imaging examination for diagnosis and treatment. These two examinations should be performed 3–7 days after the end of vaginal bleeding
- Other imaging examinations include CT and MRI. They are applicable to the patients with suspected tumor or other space-occupying lesions according to medical history, physical examination, and/or auxiliary examination to confirm the diagnosis
Medical history collection
Male medical history should focus on their sexual intercourse, marital history, and presence of systemic diseases, specialized diseases, or other risk factors that may affect fertility [Table S2].
Physical examinations in male partner include general and specific reproductive system examination.
- Physical development and nutritional status include height, weight, blood pressure, trunk-to-limb ratio, olfactory function, and secondary sex characteristics (e.g., prominentia laryngea, hair distribution, and feminization of male breasts).
- Examinations of the reproductive system need to confirm the followings:
- Whether there is phimosis or redundant prepuce, hypospadias, severe penis curvature, scar, sclerotic plaque, neoplasm, ulcer, or abnormal urethral secretion;
- The shape, volume, and texture of the testis, as well as whether there is incomplete testicular descent, ectopic, or retracted testis
- Whether epididymis is palpable, and whether there is any cyst, nodule, or tenderness
- Whether the spermaducts are palpable and complete, and whether there is any thickening, nodules, or tenderness
- Whether there is scrotal mass, varicocele and grade, hernia, scar, or lymphadenopathy in the inguinal region
- Whether the size and texture of the prostate is normal; whether there is any nodule or tenderness; whether the seminal vesicle is palpable and with tenderness or not.
- Semen analysis should be a routine examination for the male partner of an infertile couple and be performed 2–3 times to obtain baseline data. The test should be performed 2–7 days after ejaculation and be at similar time for each time. The result should be considered comprehensively with the clinical characteristics. It can fluctuate in a relatively large range for any individual. Therefore, it is not the only criteria for infertility, and the range of each parameter is only a reference for the evaluation of male fertility. Men with results below the lower limit of the reference range are not absolutely infertile. In addition, considering the difference between regions or laboratories, each lab should establish its own reference range [Tables S3] and [Table S4]]
According to sperm concentration, patients with oligozoospermia are divided as followings: (1) Mild to moderate level: the sperm concentration is within the range of 5–15 × 106/mL for 2–3 consecutive standard semen analysis. (2) Severe level: the sperm concentration is 1–5 × 106/mL for 2–3 consecutive standard semen analysis. (3) Extremely severe level: the sperm concentration is less than 1 × 106/mL after 2–3 consecutive standard semen analysis. (4) Cryptozoospermia: the spermatozoa can be only observed in the sediment pellets after centrifugation but not in the fresh semen samples
- Hormone detection. Serum hormone detection should be considered only when the patient has the following manifestations: (1) Sperm concentration is lower than 10 × 106/mL. (2) Sexual dysfunction. (3) Other clinical manifestations suggesting endocrine diseases. Reproductive hormone detection should include at least FSH and testosterone. If the testosterone level is reduced, the patient should be reexamined, and the LH and prolactin levels must be further detected [Table 1]
- Ultrasound examination of the reproductive system: When the examination of the reproductive system reveals suspected abnormalities, relevant ultrasound examinations involving prostate, seminal vesicle, testis, epididymis, blood flow in scrotum, and/or spermatic cord should be performed
- Other examinations
- Urine examination after orgasm. It is applicable to patients without semen excretion or with semen volumes of less than 1 mL after orgasm (except for those with hypoplasia of the bilateral spermaducts or clinical manifestations of hypogonadism) to confirm the presence of retrograde ejaculation
- Antisperm antibody in seminal plasma is only a reference for immune infertility but not be considered as an independent criteria
- Genetic screening: Karyotype analysis and Y chromosome microdeletion test are applicable to patients with azoospermia or severe oligozoospermia. The screening of CFTR gene is applicable to patients with azoospermia accompanied with unilateral or bilateral spermaduct agenesis. Kal gene screening is applicable to patients with suspected Kallmann syndrome
- Imaging examination of the hypothalamus–pituitary region is applicable to patients with hyperprolactinemia and gonadotropin secretion insufficiency
- Diagnostic testicular biopsy is suitable for patients with azoospermia to evaluate the spermatogenic function of the testis and distinguish between obstructive and nonobstructive azoospermia.
| Diagnosis|| |
The key point of diagnosis is to find out the etiology. Couples who meet the definition of infertility, have a medical history relative to infertility (e.g., oligomenorrhea or amenorrhea, known or suspected uterine, ovarian or pelvic lesions, Stage III to IV endometriosis, and suspected subfertility of men), or with female partner's age above 35 years old are suggested to consult a doctor and undergo relevant evaluation. Based on the results of semen analysis, gynecological examination, ovulation monitoring, hormone test, and examination of fallopian tube, classification of female factors (ovulation disorders and pelvic factors), male factors, or unexplained infertility can be draw out first. Then, according to the positive findings of medical history and clinical manifestations, other targeted auxiliary examinations are further selected to fully determine the etiology [Figure 1].
|Table 1: Clinical significance of basal reproductive hormone levels in male|
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Recent changes in mental health, diet, weight, environment, living habits, systemic diseases, and medication are important indicators. Irregular menstrual cycle (cycle ≥35 days or <26 days) or amenorrhea and ovulation evaluation can determine whether ovulation dysfunction exists. For individuals diagnosed with ovulatory dysfunction, the etiology can be determined by the combination of the positive medical history, clinical manifestations, and targeted auxiliary examination.
A medical history of infection or surgery in the genital tract, pelvic cavity, and abdominal cavity, history of infectious-disease such as tuberculosis and sexually transmitted diseases, usage of intrauterine device, as well as history of pregnancy, childbirth, and relevant complications are important indications for pelvic factors. Symptoms and signs of primary diseases (e.g., pelvic and abdominal pain, low-grade fever, dysmenorrhea, and associated symptoms), and results of auxiliary examinations can determine the presence of pelvic factors. For patients with pelvic factors, the etiology can be determined by targeted auxiliary examinations such as laparoscopy, hysteroscopy, CT, or MRI.
Medical history and physical examination can determine the presence of male factors and distinguish between primary and secondary infertility. Then, the etiology should be identified through other auxiliary examinations including semen analysis, testicular histopathological examination, hormone test, and ultrasound examination.
Unexplained infertility is a kind of exclusive diagnosis that can be diagnosed only if no abnormality is identified in the semen analysis, ovulation monitoring, gynecological examination, or fallopian tube patency examination. If necessary, laparoscopy can be used for diagnosis. For young unexplained infertile couples with normal ovarian function and less than 3 years of infertility history, intrauterine artificial insemination can be performed for 3–6 cycles as a therapeutic diagnosis.
Supplementary information is linked to the online version of the paper on the Reproductive and Developmental Medicine website.
We are grateful for the guidance and support of more than 90 experts from medical institutions at all levels in China.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| Supplementary Information|| |
Li-Ping Ding (Weifang Maternal and Child Health Hospital), Yan-Ping Ma (The First People's Hospital of Yunnan Province), Zhuo-Ran Wang (The First Affiliated Hospital of Harbin Medical University), Shu-Yu Wang (Beijing Obstetrics and Gynecology Hospital, Capital Medical University), Heng-Cai Wang (Jinan Central Hospital), Bin Wang (Liaocheng People's Hospital), Rui Wang (Beijing Tiantan Hospital, Capital Medical University), Hui-Ying Fang (Centro Hospitalar Conde de São Januário), Xiao-Hui Deng (Qilu Hospital of Shandong University), Guang-Xiu Lu (Reproductive and Genetic Hospital of CITIC-Xiangya), Hong Ye (Chongqing City Institute of Reproduction and Genetics), Bi-Lv Ye (The First Affiliated Hospital of Wenzhou Medical University), Qin-Jie Tian (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Yan Qiu (The First Affiliated Hospital of Chongqing Medical University), Yun Feng (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine), Yan-Ping Kuang (Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine), Juan-Zi Shi (Shaanxi Maternal and Child Health Hospital), Wen-Yu Qu (Shenyang Women's and Children's Hospital), Chun-Ling Gang (Dezhou People's Hospital), Dong-Yi Zhu (Linyi People's Hospital), Gui-Jin Zhu (Tongji Medical College, Huazhong University of Science and Technology), Qiong-Fang Wu (Jiangxi Maternal and Child Health Hospital), Song Quan (Nanfang Hospital, Southern Medical University), Guang-Lun Zhuang (The First Affiliated Hospital, Sun Yat-sen University), Feng-Hua Liu (Guangdong Maternity and Child Health Hospital), Rui-Zhi Liu (The First Bethune Hospital of Jilin University), Xiu-Juan Qi (The Affiliated Hospital of Qingdao University), Liang-Zhi Xu (The West China Second University Hospital of Sichuan University), Xiu-Qin Sun (Affiliated Hospital of Jining Medical University), Xiao-Xi Sun (Shanghai JI-AI Genetics and IVF Institute), Hai-Xiang Sun (Nanjing Drum Tower Hospital, Nanjing University Medical College), Lei Sun (Hong Kong Sanatorium and Hospital), Ya-Zhong Ji (Tongji Hospital of Tongji University), Mahinur Niyaz (Xinjiang Uiger Municipal People's Hospital), Da-Jin Li (Obstetrics and Gynecology Hospital of Fudan University), Bing Li (Guangzhou Institute of Obstetrics and Gynecology), Hong Li (Suzhou Municipal Hospital), Ying Li (Heze Municipal Hospital), Shang-Wei Li (The West China Second University Hospital of Sichuan University), Jian Li (Xiamen Maternity and Child Health Hospital), Yuan Li (Beijing Chao-Yang Hospital, Capital Medical University), Mu-Jun Li (The First Affiliated Hospital of Guangxi Medical University), Fang Lian (The Affiliated Hospital of Shandong University of Traditional Chinese Medicine), Hong-Mei Xiao (Reproductive and Genetic Hospital of CITIC-Xiangya), Xiao-Ke Wu (The First Affiliated Hospital of Heilongjiang University of Chinese Medicine), Rui-Fang Wu (Peking University Shenzhen Hospital), Yu Wu (International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University), Fang-Fang He (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Shu-Hua Zou (Qingdao Women and Children's Health, Qingdao University), Ai-Guo Sha (Chenggong Hospital Affiliated to Xiamen University), Huan Shen (Peking University People's Hospital), Yun-Shan Zhang (Tianjian Central Hospital of Gynaecology Obstetrics), Yi-Wen Zhang (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Yi.Wen Zhang (Weihai Women and Childrenfs Hospital), Xiao.Yu Zhang (Yantai Mountain Hospital), Song.Ying Zhang (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine), Bo Zhang (The Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region), Ling Zhang (Anhui Women and Child Health Care Hospital), Ling Zhang (Jinan Maternity and Children Health Care Hospital), Shi.Ling Chen (Nanfang Hospital, Southern Medical University), Xiu.Juan Chen (The Affiliated Hospital of Inner Mongolia Medical University), Gui.An Chen (Peking University Third Hospital), Xiao.Guang Shao (Dalian Obstetrics and Gynecology Hospital), Xue.Qing Wu (Childrenfs Hospital of Shanxi), Ge Lin (Reproductive and Genetic Hospital of CITIC.Xiangya), Cong.Rong Zhou (The Affiliated Hospital of Guizhou Medical University), Mei.Ling Zheng (First Hospital of Shanxi Medical University), Peng.Sheng Zheng (First Affiliated Hospital of Xifan Jiao Tong University), Jun.Zhao Zhao (The First Affiliated Hospital of Wenzhou Medical University), Jun.Li Zhao (General Hospital of Ningxia Medical University), Xiao.Ming Zhao (Renji Hospital, Shanghai Jiao Tong University School of Medicine), Cui.Fang Hao (Yantai Yuhuangding Hospital), Ying Zhong (Chengdu Maternal and Child Health Hospital), Li.Hui Hou (First Affiliated Hospital of Heilongjiang University of Chinese Medicine), Hong Jiang (The 105th Hospital of PLA), Yuan.Qing Yao (Chinese PLA General Hospital), Kang.Shou Yao (Zhejiang Research Institute for Family Planning Science and Technology), Xiao.Hong Dang (Qinghai Provincial Peoplefs Hospital), Ya.Li Ni (Gansu Provincial Maternal and Child Health Care Hospital), Xian Xu (General Hospital of Ningxia Medical University), Yong.Ping Xu (The Second Hospital of Shandong University), Ming.Juan Xu (Changhai Hospital, Naval Military Medical University), Su.Xin Xu (The Second Hospital of Hebei Medical University), Yao.Hong Xu (The Second Hospital of Jilin University), Shi.You Gao (Hunan Provincial Maternal and Child Health Care Hospital), Xue.Feng Huang (The First Affiliated Hospital of Wenzhou Medical University), Yun.Xia Cao (Anhui Medical University), Yan.Guo Cui (Zibo Maternal and Child Health Care Hospital), Qun Lu (Peking University Peoplefs Hospital), Han.Wang Zhang (Tongji Medical College, Huazhong University of Science and Technology), Xiao.Mei Zhang (The First Peoplefs Hospital of Yunnan Province), Yong Zeng (Shenzhen Zhongshan Urology Hospital), Xiao.Ming Teng ( hanghai First Maternity and Infant Hospital)
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