Typical cases
Case 1
Diabetes mellitus causing non-ejaculation: patient Jumoumou, born in 1984, lived with his spouse (born in 1984) for more than 4 years, no contraception and no fertility; type I diabetes mellitus for 10 years, using insulin to control blood sugar; sexual erectile function is still possible, in the last three years progressive ejaculation volume decreased to non-ejaculation, but the presence of orgasm and ejaculation sensation. Masturbation also does not ejaculate, and there is no seminal emission. Blood pressure and lipids were normal. No history of surgical trauma. The secondary sexual characteristics were normal, and no abnormalities were found in the epididymal testicular vas deferens. Sex hormone level was normal. The urine test after masturbation was performed in a foreign hospital and no semen was found.
The urine test after masturbation was performed again in our hospital, and still no sperm was found. Sex hormone level was normal. In September 2012, he underwent a caudal epididymal puncture and had his sperm frozen after a complete examination at our center.
Case 2
Retrograde ejaculation due to diabetes mellitus: The patient (31 years old) and his spouse (29 years old) got married in 2004, and his spouse had a spontaneous abortion in early pregnancy in 2005, and then did not have any contraception. In the past 5 years, he had normal erection, but delayed ejaculation, low ejaculation volume or even no ejaculation, ejaculatory sensation and ejaculatory orgasm. Sex hormones PRL and T levels were in normal range. External epididymal puncture only revealed a few immobile sperm. The testicular development was normal and the epididymal vas deferens was normal. The urinalysis after masturbation showed motile spermatozoa and a total of 20 million forward-moving spermatozoa. He denied any history of diabetes mellitus. He was referred to the endocrinology department for outpatient examination of fasting glucose 15 mmol/L. He was diagnosed with type II diabetes mellitus, and after six months of blood glucose control, retrograde ejaculation was still present. He came to the hospital for intrauterine insemination (IUI) treatment.
Analysis idea
In the case of ejaculation disorder (non-ejaculation, retrograde ejaculation), attention should be paid to the distinction between primary and secondary ejaculation disorder, whether the erectile function of the penis is normal, whether it is accompanied by ejaculatory sensation and orgasm, and whether there is seminal emission. The main causes of ejaculation are neurological, such as spinal cord injury, cauda equina, retroperitoneal lymph node dissection, colorectal surgery, multiple sclerosis, autonomic neuropathy (diabetes); pharmacological causes are mainly anti-hypertensive drugs, antipsychotics, and antidepressants.
In addition to the above two causes of retrograde ejaculation, there are also congenital hemitrigone dysfunction, bladder exstrophy, bladder neck removal, prostatectomy resulting in incomplete closure of the bladder neck; ectopic ureteral cyst, urethral stricture, urethral valves, posterior urethral abnormalities due to spermatogonial hypertrophy. The specific etiology can be analyzed in detail from the following points.
Medical history The patient must be examined in detail for history of fertility, diabetes, neuropathy, trauma, genitourinary tract infection, history of surgery and history of medication use. Particular attention should be paid to the patient’s urination and ejaculation characteristics (presence of nocturnal seminal emission, ejaculation in specific circumstances mainly referring to whether masturbation is possible, primary or secondary, developmental history) and sexual physiology (education, affection between sexual partners, previous pre-existing psychological trauma, previous psychotherapy).
Physical examination Detailed physical examination of the genitourinary system, endocrine system, and vascular nervous system. rectal finger examination is also required for patients over 50 years of age. Genital examination, anal examination of the prostate, bulbocavernosus muscle reflex and anal sphincter tone are necessary.
Post-ejaculatory urinalysis The presence or absence of partial or complete retrograde ejaculation can be determined; simply for diagnostic purposes the urine can be alkalinized without oral baking soda, requiring the patient to abstain from sex for 3-5 days, masturbate for 30 minutes after urination to extract sperm, and then empty the bladder to collect all urine for microscopic examination, either directly by microscopy or after centrifugation.
Laboratory tests should include assessment of blood glucose and plasma testosterone levels, combined with tests for prolactin and lipid metabolism, and transrectal ultrasound examination of the seminal vesicle glands, ejaculatory ducts, and prostate gland if necessary.
Treatment
The couple with diabetes mellitus-induced ejaculation underwent epididymal frozen sperm ICSI treatment at the hospital in January 2013, after routine ICSI pre-procedure preparation. After the usual ICSI preparation, a short-acting and long-acting ovulation promotion protocol was selected according to the condition of the couple, and the follicles were monitored continuously by ultrasound. Fourteen eggs were obtained, 12 of which were mature. After resuscitation of the epididymal frozen sperm, ICSI was performed and 9 were normally fertilized, resulting in 9 transferable embryos.
The couple with retrograde ejaculation due to diabetes mellitus underwent IUI treatment at our center from September to November 2013 and had three cycles of treatment.IUI treatment plan: Iodine oil imaging of the uterine tubes of the spouse confirmed bilateral patency of the lateral fallopian tubes and ultrasound monitoring of the natural cycle with dominant follicle development and ovulation. IUI was proposed for the natural cycle according to the spouse’s condition. ultrasound continuous follicle monitoring, after the dominant follicle developed and matured, intramuscular hCG 5 000 IU was injected and IUI was performed in the afternoon of the next day after hCG injection.
Alkalinization protocol for urine: 4 g of sodium bicarbonate was placed in 250 ml of water and administered orally around 6:00 to 7:00 a.m. that morning, while the patient was instructed to drink more water, which would lower the osmotic pressure of the urine.
The next morning, collect the sperm in urine, empty the bladder urine, ejaculate 20-30 minutes later, collect the urine by rapid centrifugation at 500g/min, leave the precipitate about 1ml, then screen the sperm by density gradient centrifugation, then wash with HTF-HEPES 2 times. The time for sperm preparation and IUI should be minimized. Record of the third IUI sperm treatment: Before treatment: semen volume (urine after masturbation): 30 ml, sperm concentration 10 million/ml, proportion of forward-moving sperm 25%. After treatment: sperm suspension: 0.5 ml, sperm concentration 15 million/ml, percentage of forward moving sperm 55%.
IUI operation and luteal support: The female partner was placed in a cystotomy position, and after exposing the cervix, a 1 ml syringe was connected to a disposable insemination tube (COOK), and the sperm suspension was aspirated and slowly injected into the uterine cavity with the hips elevated in a supine position for about 20 min. routine luteal support was performed after the operation. One of the spouses had a successful pregnancy after the third IUI and has now given birth to a healthy child.
Lessons learned
It is important to discuss the pros and cons of various treatment options with the patient before initiating treatment for diabetogenic ejaculation disorder and to provide a thorough explanation of the diagnostic treatment strategy. Patients may often be unaccompanied by a sexual partner at the initial visit, but physicians should make an effort to bring the spouse to the patient’s return visit. The spouse should be advised to go to a specialist for the necessary consultation. Counseling of the patient and his or her sexual partner is also essential.
Infertility due to ejaculation disorders that require treatment with assisted reproductive technology. When making a decision, the age of the patient and his or her partner; the psychological problems of the patient and his or her partner; the wishes of the couple and their acceptance of different methods of conception; and concomitant diseases should be taken into account.
The clinic should give high priority to patients with manifestations of ejaculatory dysfunction to give high priority to the presence of combined diabetes mellitus. Invasive tests and surgical procedures such as vesiculoscopy, spermography, testicular epididymal aspiration for sperm extraction should not be used in cases where the diagnosis is unknown.
Image data
Case review
In the past 20 years, China’s national economy has developed rapidly, people’s living standards have improved rapidly, the disease spectrum in China has changed significantly, and chronic non-communicable diseases, including diabetes, have gradually become an important social health problem. According to the information in 1996, diabetes and impaired glucose tolerance patients in China accounted for 3.2% and 4.8% of the total population over 20 years old respectively, which means that the population with abnormal blood sugar is close to 100 million.
Diabetes mellitus is a group of metabolic diseases characterized by elevated blood glucose levels. The pathophysiological mechanism that causes elevated blood glucose is defective insulin secretion and/or defective insulin action. Significantly elevated blood glucose may be accompanied by polyuria, polydipsia, weight loss, sometimes polyphagia and blurred vision. Among the chronic complications, diabetic peripheral neuropathy is one of the most common complications of diabetes mellitus, with a prevalence of up to 70%-90%.
It can involve sensorimotor and autonomic nerves, and the pathological changes are mainly demyelination and or axonal degeneration of peripheral nerves. Diabetic peripheral neuropathy can lead to ejaculatory disorders. Diabetes also causes penile erectile dysfunction through multiple mechanisms leading to neurological and vascular lesions.
Diabetes mellitus causing ejaculation disorder is firstly a comprehensive treatment for diabetes mellitus, including diet control, exercise, blood glucose monitoring, diabetes mellitus self-management education and medication; at the same time, it should include a comprehensive treatment of measures such as glucose lowering, blood pressure lowering, lipid regulation and changing bad habits such as smoking cessation.
The next treatment is for ejaculatory dysfunction. If combined with erectile dysfunction, priority should be given to erectile dysfunction. Retrograde ejaculation in the absence of spinal cord injury, anatomical malformation of the urethra, or pharmacological causes, pharmacological treatment can be attempted first to induce it in a prograde ejaculation. Some retrograde ejaculation may be the result of para-aortic lymph node dissection and disorders of the vegetative nervous system. Pharmacological treatment may be alpha-adrenergic sympathetic excitatory drugs. Patients may also be advised to have sex when their bladder is full to increase bladder neck pressure.
For patients who do not ejaculate, vibratory stimulation can induce the ejaculatory reflex, which requires an intact lumbosacral spinal cord, and vibratory stimulation is more effective for spinal cord injuries above T10. Vibratory stimulation of the penis is the first-line therapy for ejaculation caused by neuropathy. If vibratory stimulation fails to retrieve sperm, an electrical stimulator is available. It is used to cause the patient to ejaculate by electrically stimulating the nerves around the prostate with a probe inserted into the anus, even when the patient’s reflex arc is incomplete.
Unless the patient has a complete spinal cord injury, anesthesia is usually required. Electrical stimulation for sperm retrieval can result in successful retrieval in 90% of patients, but about one-third have retrograde ejaculation. Most patients who do not ejaculate still need to resort to assisted reproductive techniques due to poor semen quality. IUI is preferred. Patients who fail IUI or have poor semen quality may consider IVF or ICSI treatment after sperm extraction with penile vibratory stimulation or electrical stimulation devices.
If electrical stimulation for sperm retrieval fails or cannot be performed, sperm can be obtained by epididymal puncture. If epididymal puncture is used for sperm retrieval, the puncture site is different from epididymal obstruction and congenital vas deficiency such as puncture from the head of the epididymis, and the needle should be inserted from the tail of the epididymis. In epididymal obstruction or congenital vas deficiency, sperm quality is the opposite of normal; high quality sperm are present in the proximal part of the epididymis and very poor quality in the most distal part; this “reversal of viability” can be expected to be found in the male genital tract of obstructed men, as the testes are constantly producing sperm in the most distal region of the system. The resorption of these spermatozoa is an active process.
Most distally obstructed epididymides contain swollen yellow tubules with lumens filled with macrophages that have engulfed senescent and degraded spermatozoa. Therefore, sperm must be extracted from the proximal end of the obstructed epididymis and from the testis to obtain high-quality motile sperm. In fact, it has been found that the density of motile sperm in obstructed epididymal fluid can be as high as 1×109/ml, whereas in patients with non-ejaculation, the vas deferens is open and the sperm storage site is the caudal part of the epididymis, from which it is easier to obtain a higher number and more viable sperm. If sperm retrieval fails, it is important to suspect the presence of epididymal obstruction or testicular failure, at which point testicular puncture can be performed to retrieve sperm.