RU2519185C1 - Method for prediction of male reproductive function normalisation following varicocelectomy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: what is involved is the pre-operative ejaculate values: sperm concentration, percentage of movable sperm cells coated by sperm-reacting antibody, production of sperm active oxygen intermediates. The values of sperm concentration 0.01-45 mln/ml, percentage of sperm cells coated by sperm-reacting antibody less than 50%, production of sperm active oxygen intermediates more than normal values are considered to be prognostically favourable.

EFFECT: method enables the high accuracy prediction of the male reproductive function recovery.

1 ex, 2 tbl

Description

The invention relates to medicine, namely to urology, andrology and reproductology, and can be used to predict the effectiveness of subsidizing operations to restore reproductive function with varicocele.

It is known that about 15% of couples are infertile, and in half the cases this is due to a violation of sperm quality [1]. About a quarter of these men are diagnosed with varicocele - spermatic vein dilation [2].

A common method for treating men from infertile couples with varicocele is ligation of the spermatic veins [1, 2]. However, a meta-analysis of the studies performed shows that data on the positive effect of such operations are doubtful [3]. The EAU Guide to Urology [2] lists factors that can be considered predictors of improved sperm quality after varicocelectomy: a duration of infertility of more than 2 years and clinically expressed forms of varicocele. However, the improvement in sperm quality after surgery remains uncertain.

The objective of the present invention is to increase the effectiveness of subsidizing operations for varicocele in men from infertile couples.

This problem is solved by performing special sperm studies prior to surgery, which serve as predictors of improving ejaculate quality and restoring male fertility. In the absence of these signs, surgery should be considered less effective and additional treatment methods should be recommended: specific drug therapy (hormonal stimulation, antioxidants, etc.) and / or assisted reproductive technologies (including IVF).

The advantages of the proposed method are confirmed by the treatment of 172 men with varicocele from infertile couples with various impaired sperm quality. The diagnosis of varicocele was made on the basis of a physical examination and ultrasound examination using dopplerometry. Ejaculate quality was evaluated in accordance with WHO recommendations [4]. Varicocelectomy was performed: microsurgically from a subinguinal mini-access (n = 84), laparoscopically (n = 68), high ligation from the retroperitoneal access (n = 20); it is known that in the absence of relapse, the technique of the operation does not affect its results [1, 2, 3]. The results of the operation are retrospectively evaluated taking into account:

1) factors considered as a prototype - the duration of infertility is more than 2 years and clinically pronounced forms of varicocele [2];

2) according to the proposed method, the inclusion criteria considered the concentration of sperm in the ejaculate 0.01-45.0 million / ml, motile sperm coated with antisperm antibodies (ASAT) - less than 50%, the production of reactive oxygen species (ROS) in the ejaculate is greater than the standard values (0.65 mV / s using the chemiluminescence method).

Patients with azoospermia and reproductive tract infections were excluded from the study.

The data obtained are presented in tables 1 and 2, illustrated by a clinical example.

Table 1 The initial quality indicators of the ejaculate in groups of patients isolated from the total population based on the criteria of the proposed method and the prototype method, n and M +/- S No. Indicators The proposed method Prototype method [2] R one The number of patients, n 94 132 - 2 Age years 30.8 ± 4.9 31.4 ± 5.1 > 0.05 3 Varicocele subclinical 9 0 <0.01 four Varicocele +1 40 66 > 0.05 5 Varicocele +2 42 59 > 0.05 6 Varicocele +3 3 7 > 0.05 7 Volume ml 3.76 ± 1.60 3.68 ± 1.6 > 0.05 8 Concentration, mln / ml 13.8 ± 11.4 34.6 ± 40.1 <0.001 9 Progressive Mobility,% 27.3 ± 16.1 29.2 ± 17.1 > 0.05 10 Pathological forms,% 75.3 ± 19.0 74.4 ± 20.9 > 0.05 eleven Covered with antisperm antibodies (MAR-test),% 6.0 ± 10.1 29.9 ± 37.8 <0.001 12 Sperm quality index - the estimated number of progressively motile and morphologically normal sperm in the ejaculate, million 4.7 ± 7.2 10.8 ± 18.75 <0.001

Note: p is the probability of an erroneous deviation of the null hypothesis of differences in the indicators of groups formed in accordance with the proposed method and the prototype method.

table 2 The advantages of the proposed method of examination, increasing the normalization of the reproductive function of men after varicocelectomy No. Options The proposed method Prototype method F21 R one Patients who showed an improvement in ejaculate quality by sperm quality index, n (%) 80/94 (85.1%) *** 96/132 (72.7%) *** <0.05 2 Patients with normozoospermia according to WHO 2010 > 0.05 - before surgery 16/94 (17.0%) ^A 29/132 (22.0%) ^B - after operation 42/94 (44.7%) *** 48/132 (36.4%) * 3 Sperm quality index changes - sperm count +12.1 million (+253.8%) *** +11.2 million (+103.6%) *** <0.05

zoids with progressive motility and normal morphology in the ejaculate, million (%) four Autoimmune patients 11/14 18/60 <0.01 reactions against sperm, in which there was a decrease in the percentage of cells coated with antisperm antibodies, n (%) (-78.5%) (-30.0%) 5 Percentage changes -2.5% - 0.73% > 0.05 motile sperm coated with antisperm antibodies, absolute changes (%) (-16.51%) (-2.45%) 6 The number of advances 35/94 29/132 <0.02 pregnancies within 12 months (%) (37.2%) (22.0%)

Note: 3 months after surgery; patients with relapse are excluded from the statistical analysis; p is the probability of an erroneous deviation of the null hypothesis of the difference between the proposed method and the prototype method; * - differences in the indicator before and after surgery are statistically significant with p <0.05, *** - p <0.001; ^A - patients with impaired acrosomal reaction, overproduction of reactive oxygen species or idiopathic infertility in the presence of normozoospermia; - Patients with immune infertility, a violation of the acrosomal reaction or idiopathic infertility on the background of normozoospermia.

Example (IS No. 3 515/03):

Patient A.S. 32 years old complained of a lack of pregnancy for 4 years with regular sex without contraception. From the anamnesis: systemic and venereal diseases, harmful factors, scrotal organ injuries denied. Examined: testicles of normal sizes and consistency, bilateral varicocele - III degree on the left and I degree on the right. Ejaculate (02.17.2003): volume 3.6 ml; pH 7.0; liquefaction of 20 min, the concentration of sperm 24 million / ml; mobile categories A - 2%, B - 47%, C - 9%, D - 42%; viability of 58%; pathological forms of 56%, including heads - 30%, necks - 7%, tail - 4%, mixed - 15%; spontaneous acrosomal reaction - 47%, induced - 19%, inducibility - 28%; There are no ASATs (MAR IgG = 0%), ROS - 16.02 mV / s. Hormones: LH - 6.8 mIU / L; FSH - 11.2 mIU / L; PRL - 185 mIU / L; testosterone - 28.5 nM / l; cortisol - 371 nM / L.

Diagnosis: primary infertility, varicocele bilateral, normozoospermia, oxidative stress, disturbances in the acrosomal reaction of spermatozoa.

A laparoscopic varicocelectomy was performed on both sides (06.24.2003).

6 months after surgery (December 2003), pregnancy occurred. According to sperm research (01/20/04 - 6 weeks of pregnancy): volume 4.0 ml; pH 7.0; liquefaction for 20 minutes, sperm concentration 32 million / ml; mobile categories A -2%, B - 72%, C - 6%, D - 20%; viability of 80%; pathological forms of 69%, including heads - 17%, necks - 8%, tail - 4%, mixed - 40%; spontaneous acrosomal reaction - 2%, induced - 40%, inducibility - + 38%; There are no ASATs (MAR IgG = 0%), ROS 4.25 mV / s - i.e. after bilateral varicocelectomy, the oxidative stress of sperm decreased, the concentration and motility of sperm increased, the acrosomal reaction normalized, and spontaneous pregnancy occurred.

The data presented indicate that the differential laboratory inclusion criteria, according to the proposed method, allow, with the same degree of varicocele and the patient's age, to obtain after varicocelectomy a more significant increase in quantitative indicators of spermogram (85% of cases; 95% CI 0.78-0.92), a higher percentage of cases achieve normozoospermia (45% of cases; 95% CI 0.35-0.55) and pregnancy (37% of cases; 95% CI 0.27-0.47).

Information sources

1. Sukhikh G.T., Bozhedomov V.A. MEN'S INFERTILITY. A practical guide for urologists and gynecologists. Textbook for the system of postgraduate professional education of doctors. M .: "Eksmo", 2009 - S.168-177: ill. - Medical practice.

2. GUIDELINES ON MALE INFERTILITY / A. Jungwirth, T. Diemer, G.R. Dohle, A. Giwercman, Z. Cora, C. Krausz, H. Tournaye. - © European Association of Urology 2012, - C.30-32.

3. Evers JH, Collins J, Clarke J. Surgery or embolisation for varicoceles in sub fertile men. Cochrane Database Syst Rev 2009 Jan 21; (1): CD000479.

4. WHO laboratory manual for the examibation and processing of human semen. 5th ed. Geneva: WHO; 2010.271 p.

Claims (1)

A method for predicting the normalization of male reproductive function after varicocelectomy, including preoperative assessment of the following ejaculate indicators: sperm concentration, percentage of motile spermatozoa coated with antisperm antibodies, sperm production of active oxygen species; They consider prognostically favorable: sperm concentration of 0.01-45 million / ml, the percentage of sperm coated with antisperm antibodies is less than 50%, the production of active oxygen in semen is higher than standard values.