Types Of Infertility Research Articles

Features of the psychoemotional state of pregnant women with different types of infertility in history

The objective: to study the features of the psycho-emotional state of pregnant women with different types of infertility in the anamnesis.Materials and methods. A study of psycho-emotional status in 127 pregnant women 20–49 years old, of which 97 women had a history of different forms of infertility and 30 pregnant women without a history of infertility, was carried out. The distribution of pregnant women into the groups was based according to the factor of infertility: I group included 35 pregnant women with a history of endocrine infertility, II group – 37 persons with a history of tubal origin infertility, III group – 25 pregnant women with a history of combined infertility (tubal and endocrine factors), IV group (control group) – 30 healthy pregnant women who had no history of infertility.L. Reeder psychosocial stress scale and Luscher color test were used to assess the psycho-emotional state.Results. The obtained data of L. Reeder psychosocial stress scale demonstrated that that in the I group the high level of psychosocial stress was found in 34.3 % of pregnant women, the moderate level – 37.1 % persons, in the II group – in 29.7 % and 37, 8 % individuals, respectively, in the III group – 56 % and 24 %, in the IV group – 6.7 % and 10 %. The results of the Luscher color test showed that high level of anxiety had 57.1 % in the I group, 59.5 % – in the II group, 68% – III group, and, 6.7 % – IV group. The indicators of pregnant women of groups I, II, III are marked by a high percentage of the 6th-8th positions – 57.1 %, 59.5 % and 68 % versus 6.7% of the persons in the IV group. This indicates a high level of anxiety in the patients with a history of infertility. Only 15 % of women in the I and II groups and 8 % – in the III group feel confident.The results of the Luscher test presented the highest number of women with the highest score of anxiety in the III group (68 %), which is 7 times more than in the IV one; 93.3 % of patients in the IV group had low and moderate levels of anxiety.Conclusions. Pregnant women with a history of infertility are in the group with a high level of anxiety and markedly unstable psycho-emotional state. The highest levels of psycho-emotional disorders are determined in women with a history of combined infertility.

Circular RNAs: Novel Biomarkers in Spermatogenesis Defects and Male Infertility.

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs involved in several cellular and biological processes, including gene expression regulation, microRNA function, transcription regulation, and translation modification. Therefore, these non-coding RNAs have important roles in the pathogenesis of various diseases. Male infertility is mainly due to abnormal sperm parameters such as motility, morphology, and concentration. Recent studies have confirmed the role of circRNAs in spermatogenesis, and the expression of several circRNAs is confirmed in seminal plasma, spermatozoa, and testicular tissue. It is suggested that deregulation of circRNAs is involved in different types of male infertility, including azoospermia, oligozoospermia, and asthenozoospermia. In the present review, we aimed to discuss the potential roles of circRNAs in spermatogenesis failure, sperm defects, and male infertility. Due to their conserved and special structure and tissue-specific expression pattern, circRNAs can be applied as reliable noninvasive molecular biomarkers, therapeutic and pharmaceutical targets in male infertility.

Mitochondrial DNA content reduction in the most fertile spermatozoa is accompanied by increased mitochondrial DNA rearrangement.

Is there an association between male fertility and spermatozoa mitochondrial DNA (mtDNA) copy number and genome rearrangements? Normal spermatozoa not only have a lower mtDNA copy number but also more DNA rearrangements than spermatozoa of men with severe oligoasthenospermia (SOA). While there is a consensus that mtDNA content is decreased in the most fertile spermatozoa, the role of mtDNA sequence alteration in male infertility is unclear. High-throughput sequencing, which allows an exhaustive analysis of mtDNA rearrangements and mutations, could be helpful in this context, but has yet to be used. This is an observational study of semen samples obtained from 44 men undergoing ART at an academic infertility centre in France, from October 2018 to November 2020. The men were classified into two groups: 20 men in the SOA group and 24 men with normal semen parameters in the control group. For each patient and control, mtDNA was isolated from sperm fractions from the 40% and 90% layers of the density gradient. The average mtDNA content of each sample was assessed using digital PCR. Deep sequencing was performed using next-generation sequencing. Signal processing and base calling were performed via the embedded pre-processing pipeline, the variants were analysed using an in-house workflow and a dedicated tool, based on soft-clipping, was used to study large mtDNA rearrangements. The distribution and the type of rearrangements and variants were compared between patients with SOA and controls on one hand, and between the 40% and 90% gradient layers, on the other hand. The mtDNA content of spermatozoa in the SOA group was significantly higher than in the control group (P < 0.0001). Moreover, mtDNA content was significantly higher in spermatozoa from the 40% layer (the most fertile spermatozoa) compared to the 90% layer, both in the SOA (P = 0.02) and the control group (P < 0.0001). The frequency of large mtDNA deletions and duplications was significantly higher in the control group (P = 0.002). Most of these rearrangements are potentially related to DNA breaks and their number was reduced by the removal of the linear mtDNA from the samples. Heteroplasmic variants were found more frequently in the SOA group (P = 0.05) and in the 40% layer (P = 0.03), but none had any obvious functional consequence. Our findings are novel and significant but should be verified in larger cohorts and other types of male infertility. Our findings suggest that sperm mtDNA rearrangements are not necessarily associated with mitochondrial dysfunction and male infertility. Instead, they seem to be concomitant with the process of mtDNA content reduction in the most potentially fertile spermatozoa. Furthermore, they refute the hypothesis that, in the case of mtDNA alteration, a compensatory mechanism allows an increase in mtDNA copy number to rectify the energy deficit. The increased frequency of mtDNA rearrangements in the most fertile spermatozoa is a novel result that offers new insight into the relation between sperm quality and mtDNA. This work was supported by Angers University Hospital (grant AOI CHU Angers 2018), Angers University and the French national research centres INSERM and CNRS. There are no competing interests. N/A.

Association between the single nucleotide variants of the mitochondrial cytochrome B gene (MT-CYB) and the male infertility

BackgroundIdiopathic male infertility can be attributed to genetic predispositions that affect sperm performance and function. Genetic alterations in the mitochondrial DNA (mtDNA) have been linked to certain types of male infertility and abnormal sperm function. Mutations in the mitochondrial cytochrome B (MT-CYB) gene might lead to some deficiencies in mitochondrial function. Thus, in the current study, we aimed to investigate the effect of mutations in the MT-CYB gene on sperm motility and male infertility.Methods and resultsSemen specimens were collected from 111 men where 67 men were subfertile and 44 were fertile. QIAamp DNA Mini Kit and REPLI-g Mitochondrial DNA Kit from QIAGEN were used to isolate and amplify the mitochondrial DNA. Followed by PCR and Sanger sequencing for the target sequence in the MT-CYP gene. Sequencing of the MT-CYB gene revealed a total of thirteen single nucleotide polymorphisms (SNPs). Eight SNPs were non-synonymous variant (missense variant) including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155. While five SNPs were Synonymous variant: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124. Among these SNPs, three variants showed a significant difference in the frequency of the genotypes between subfertile and fertile groups: rs527236194 (T15784C) (P = 0.0005), rs28357373 (T15629C) (P = 0.0439), and rs41504845 (C15833T) (P = 0.0038). Moreover, two SNPs showed a significant association between allelic frequencies of rs527236194 (T15784C) (P = 0.0014) and rs41504845 (C15833T) (P = 0.0147) and male subfertility.ConclusionThe current study showed a significant association between the MT-CYB gene polymorphisms and the development of male infertility. In particular, rs527236194, rs28357373 and rs41504845 variants were found to be the most related to the subfertility group. Further studies on larger and other populations are required to reveal the exact role of this gene in the development of male infertility. In addition, functional studies will be helpful to elucidate the molecular impact of the MT-CYP polymorphisms on mitochondrial function.

Prevalence of Overweight and Obesity among the Visitors of Prince Sultan Military Medical City

Aim: The aim of this study was to measure the commonness of obesity among the visitors of Prince Sultan military medical city (PSMMC), Hospital, Riyadh. Materials and Methods: This cross-sectional study was done from November 15, 2018, to February 15, 2019. A well-established questionnaire was prepared based on the literature. A total of 1489 participants of either sex participated in this study. The body mass index (BMI) scale measures the obesity. Reuslts: This study has revealed that obesity among the young visitor of the Prince Sultan military medical city, Riyadh, was higher than the middle age and old age people. It was also observed that obesity was more prevailing in young males than young females. There is a need to educate these young people about the foreseeable effects of obesity comprising insulin resistance, diabetes, metabolic syndrome, hyperlipidemia, hypertension, and ischemic stroke, gastroesophageal reflux, cholelithiasis, osteoarthritis, many types of cancer, infertility, impotence, and polycystic ovarian syndrome. Conclusion: The obesity awareness programs should also be conducted to lower down the percentage of obese people of the Riyadh city. Keywords: Body Mass Index, Obesity, Overweight, PSMMC Hospital. Riyadh

Reproductive outcomes after laparoscopic surgery in infertile women affected by ovarian endometriomas, with or without in vitro fertilisation: results from the SAFE (surgery and ART for endometriomas) trial

We performed a retrospective cohort study, namely “Surgery and ART for Endometriomas” (SAFE) trial (Clinical Trial ID: NCT03717870), including women who underwent laparoscopic cystectomy for endometrioma before first IVF and compared their reproductive outcomes with the ones of women without endometriosis and with unexplained infertility, tubal factor or male factor infertility. We found that women who underwent previous laparoscopic cystectomy for endometrioma had higher FSH and LH levels between the 2nd and 5th day of the cycle before IVF, required higher doses of gonadotrophins for ovarian stimulation and had a lower number of retrieved oocytes compared with other types of infertility. Nevertheless, pregnancy and delivery rates remain comparable to other causes of infertility. In addition, differences in ovarian stimulation parameters between endometriosis and other types of infertility lost significance with the increase of women’s age. These pieces of information can be considered useful to make adequate counselling about reproductive outcomes for infertile women with ovarian endometriomas and allow a proper decision-making approach shared with the patient. IMPACT STATEMENT What is already known on this subject? Although endometriomas are common findings in infertile women, whether they should be surgically removed before an in vitro fertilisation (IVF) is a long-lasting debate, and current evidence does not offer a robust background to draw firm recommendations. What do the results of this study add? Women who underwent previous laparoscopic cystectomy for endometrioma need higher doses of gonadotrophins for ovarian stimulation and have a lower number of retrieved oocytes, compared with other types of infertility. Pregnancy and delivery rates remain comparable to other causes of infertility. What are the implications of these findings for clinical practice and/or further research? These pieces of information can help to make adequate counselling about reproductive outcomes for infertile women with ovarian endometriomas and allow a proper decision-making approach shared with the patient.

Aetiologies and therapeutic management of infertility in cows reared in high altitude tribal areas of Himachal Pradesh

Infertile cows (664) reared in different tribal areas of Himachal Pradesh were examined thoroughly by rectal examination during infertility treatment camps and diagnosis of reproductive ailments was done to document the prevalence of different types of infertility. The highest prevalence was recorded for anestrus (44.27%) followed by endometritis (42.77%) and miscellaneous reproductive disorders (6.77%). Highest prevalence of anestrus conditions was recorded in Bharmour (51.72%) followed by Kinnaur (49.05%), Lahaul (47.76%) and Spiti (45.39%) areas whereas, lowest prevalence was recorded in Pangi (27.93%) region. After diagnosis, 189 cows were treated for different reproductive ailments; however, only 101 cows could be followed, and 70 responded to the treatment with success rate of 69.30%. Anestrus and endometritis were the most prevalent forms of infertility in cows of tribal areas and were successfully treated with their respective treatment regimen.

Impact of Various Parameters as Predictors of The Success Rate of In Vitro Fertilization.

Infertility is one of the major problems faced in medicine. There are numerous factors that play a role in infertility. For example, numerous studies mention the impact of the quantity and quality of mitochondria in sexual gametes. This is a narrative review of the effects of the mitochondrial genome on fertility. We searched the PubMed, Science Direct, SID, Google Scholar, and Scopus databases for articles related to “Fertility, Infertility, Miscarriage, Mitochondria, Sperm, mtDNA, Oocytes” and other synonymous keywords from 2000 to 2020. The mitochondrial genome affects infertility in both male and female gametes; in sperm, it mainly releases free radicals. In the oocyte, a mutation in this genome can affect the amount of energy required after fertilisation, leading to gestation failure. In both cases, infertile cells have substantially less mitochondrial DNA (mtDNA) copies. The effects of mtDNA on gamete fertility occur via changes in oxidative phosphorylation and cellular energy production. Also, a reduction in the number of mtDNA copies is directly associated with sex cell infertility. Therefore, evaluation of the mitochondrial genome can be an excellent diagnostic option for couples who have children with neonatal disorders, infertile couples who seek assisted reproductive treatment, and those in whom assisted reproductive techniques have failed.

Types of Infertility and Its Risk Factors among Infertile Women: A Prospective Study in Dhaka City

Background: Infertility is a global health issue, and it is a multidimensional problem with social, economic, and cultural influences. Objectives: The study aimed to determine types of infertility and their contributing factors among the respondent infertile women. Methods: This prospective cross-sectional study was conducted among infertile women visiting Sir Salimullah Medical College and Hospital, Dhaka. From January to December 2020, 111 infertile women were included and evaluated for infertility types and their contributing factors. Data were collected by face-to-face interviewing, and data were analyzed statistically. Results: Primary infertility was found among 90 (81%) and secondary infertility among 21 (18.9%). Among the direct risk factors of female infertility, ovulation failure was the majority of the cases, 74 (35.1%), and its mainly observed in primarily infertile women 58 (33.9%). These observations were statistically significant. Conclusions: Infertility should be treated as a public health problem, government and non-government organizations should develop a basic policy to create effective fertility centers.

Vitamin D indicators in pregnancy dynamics in women with different types of infertility in their history

The objective: to study the level of vitamin D in the dynamics of pregnancy in women with various types of infertility in history. Materials and methods. 127 women were examined: I group – 35 pregnant women who had a history of endocrine infertility; II group – 37 women with tubal-peritoneal infertility; III group – 30 pregnant women who had a history of tubal-peritoneal infertility with endocrine factor; IV (control) group – 25 healthy pregnant women without a history of infertility. To determine the level of 25-hydroxyvitamin D, a two-stage ELISA method was used. Results. Insufficiency and deficiency of vitamin D in the I trimester of pregnancy had 5 (20.0%) women without a history of infertility each, in the III trimester – 40% and 28% persons, respectively. Deficiency of 25-hydroxyvitamin D in the I group was detected in 15 (42.9%) patients in the I trimester and in 20 (57.1%) patients in the III trimester, in the II group – 10 (27.0%) and 17 (45.9%) persons, respectively, in the III group – 15 (50.0%) and 18 (60.0%) women, respectively.The number of patients with vitamin D deficiency during pregnancy in the groups of patients with a history of infertility was significantly higher compared with pregnant women without a history of infertility. Also, an increased rate of persons with vitamin D deficiency was determined among patients of the I, II and III groups compared with women of the IV group. Conclusions. In the dynamics of pregnancy an increase frequency of persons with insufficiency and deficiency of vitamin D was found among the women with a history of infertility, the largest rate of which was determined in pregnant women with endocrine infertility and tubal-peritoneal infertility in combination with an endocrine factor.

Spermogram and Hormone Profile Indicators Analysis Among Patients with Different Types of Male Infertility Depending on Antioxidant System Status

The objective: evaluation of interrelation between indicators of spermoplasm, androgen profile and malondialdehyde (MDA) content in spermoplasm among men with different types of male infertility. Materials and methods. 39 men at the age ranged from 24 to 45 years with different degrees of spermatogenesis and hormonal profile disorders were examined; MDA content in spermoplasm among patients who were diagnosed with «secretory male infertility» (n=7) was 23.3-38.3 μm/l, diagnosed with «excretory-toxic male infertility» (n=32) – 17.3–53.0 μm/l, therefore this group was divided into subgroups: 1 – up to 19.9 μm/l; 2 – within 20.6–29.1 mcm/l; 3 – more than 30.0 μm/l. In spermoplasm of the control group (donor sperm), this indicator was within 20.8–24.9 μm/l range. Interrelation assessment between the investigated indicators was carried out by methods of variational and correlation analysis using non-parametric statistics. Results. Studies results showed that the number of white blood cells in patients’ sperm of all groups exceeded the standard, wherein a close connection between this indicator and MDA content in spermoplasm (r=0.99 and r=0.48, with α≤0,05) was established. In groups where lipid peroxidation activity was significantly higher than control indicators, the highest percentage of men (more than 40%) with reduced sperm activity and viability was detected. Free testosterone decrease was observed among almost 70-90% of examined men, while the most significant changes were found among patients who were diagnosed with «excretory-toxic male infertility» and high MDA content in spermoplasm. A close positive connection between MDA content and sperm dilution time (r=0.79; α≤0,05) was established in group of patients who were diagnosed with «secretory male infertility», as well as the level of LH in blood (r=0.74; α≤0,05); among patients who were diagnosed with «excretory-toxic male infertility» the status of the pro-antioxidant system, which is characterized as «oxidative stress» (third subgroup), a reliable negative association was found between MDA level in spermoplasm and the level of FSH in blood (r=– 0.75; α≤0,05). Conclusions. A relation between high MDA level in spermoplasm and increase of white blood cells number in sperm was established, as well as a decrease of sperm motor activity and content of bioavailable testosterone in blood.

Зміни в системах: обміну ліпідів та вуглеводів у вагітних із різними формами безплідності в анамнезі

The most significant changes in lipid and carbohydrate exchange systems were in women with a history of endocrine and combined infertility, which is explained by their presence of risk factors, namely age, PCOS, an increased frequency of somatic pathology (metabolic syndrome, obesity, insulin resistance) complicated by the course of pregnancy. Purpose — to study changes in systems: lipid and carbohydrate metabolism in pregnant women with various forms of infertility. Materials and methods. Changes in systems were studied: lipid and carbohydrate metabolism in 127 pregnant women with various types of infertility. The distribution of pregnant women to groups is based on infertility factor: group I — 35 pregnant women with a history of endocrine infertility, group II — 37 pregnant women with a history of infertility of trumpe-peritoneal genesis, group III — 30 pregnant women with a history of combined infertility: trumpe-peritoneal genesis with endocrine, control group (IV) — 25 healthy pregnant women who did not have a history of infertility. To assess metabolic disorders, all women were measured for BP, blood levels were determined: glucose and HOMA (Homeostasis Model Assesment) index, triglycerides and high3density lipoproteins. Used: immunochemiluminescent, enzymatic colorimetric and kinetic enzymatic method. The validity for relative values was evaluated by the Fisher angular transform method. Results. Examining plasma glucose measurement data in women with different types of infertility by groups in the I and III trimesters found that in the I group, increased rates were in 5 (14.3%) patients in the I trimester and in 9 (25.7%) in the III trimester; in group III, 3 (10%) patients in the I trimester and 10 (33.3%) in the III trimester; while elevated blood sugar levels in group II women were in 3 (10%) patients in the I trimester and 10 (33.3%) in the III trimester, and in group IV none had elevated glucose levels in the I trimester and in 1 (8%) patient it increased in the III trimester. Determining the HOMA index in women with different types of infertility by groups in the I and III trimesters found that in the I group, increased rates were in 4 (11.4%) patients in the I trimester and in 5 (14.3%) in the III trimester; in group III in 3 (10%) patients in the I trimester and in 4 (13.3%) in the III trimester; while the indicator of the HOMA index in group II women did not change, both in the I trimester and III trimester and amounted to — 1 (2.7%), and in group IV no one had an increased HOMA index, both in the I trimester and III trimester. Analyzing high3density lipoprotein (HDL) measurement data in women with different types of infertility by groups in the I and III trimesters, it turned out that in the I group, 2 (5.7%) patients in the I trimester and 4 (11.4%) in the III trimester had increased rates; in group III in 3 (10.0%) patients in the I trimester and in 6 (20.0%) in the III trimester; while the HDL in women of group II did not change, both in the I trimester and in the III trimester and amounted to — 1 (2.7%), and in group IV no one had elevated HDL, both in the I trimester and in the III trimester. Conclusions. In pregnant women with a history of endocrine and combined infertility already in the first trimester, the glucose level exceeded 5.6 mmol/l in 14.3% and 10% of patients; in the III trimester, this indicator was equal to 25.7% and 33.3%, respectively. The HOMA index in the III trimester in these women was increased and was calculated in pregnant women with endocrine infertility in the past — 14.3% and in pregnant women with combined infertility — 13.3%, which was significantly higher than the indicators of patients who had tube-peritoneal infertility — 2.7%. In healthy pregnant women who did not have a history aggravated by infertility, there was no increase in the HOMA index. In pregnant women with a history of endocrine and connected infertility, the level of lipoproteins also increased by 11.4% and 20%, respectively, and triglycerides in 8.6% and 16.7% of women in the III trimester relative to pregnant women who had a history of tube-peritoneal infertility and healthy pregnant women. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: lipid and carbohydrate exchange, history of endocrine and tube3peritoneal infertility, pregnancy.

Using microRNAs as molecular biomarkers for the evaluation of male infertility.

Infertility is a multiplex disorder in the reproductive system, and men are responsible for more than half of the cases. Nowadays, semen analysis has been considered the critical assessment test to diagnose infertile men; however, it has limitations so that the cause behind infertility in 40% of infertile men is unrevealed. Weaknesses of semen assessment indicate a global need for novel and better diagnostic tools and biomarkers. MicroRNAs are short (about 18-22 nucleotide length) non-coding RNAs that control most (>60%) of our protein-coding genes post-transcriptionally. These molecules are aberrant in the body fluids, and abnormal alterations in their expression level can signify a specific disease such as infertility. Therefore, microRNAs can be novel candidate biomarkers that can diagnose different types of male infertility, including azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. This narrative review aimed to collect and sum up new papers published about the significant role of microRNAs in different male infertility categories.

The Development of Nomograms to Predict Blastulation Rate Following Cycles of In Vitro Fertilization in Patients With Tubal Factor Infertility, Polycystic Ovary Syndrome, or Endometriosis

It is well known that the transfer of embryos at the blastocyst stage is superior to the transfer of embryos at the cleavage stage in many respects. However, the rate of blastocyst formation remains low in clinical practice. To reduce the possibility of wasting embryos and to accurately predict the possibility of blastocyst formation, we constructed a nomogram based on range of clinical characteristics to predict blastocyst formation rates in patients with different types of infertility. We divided patients into three groups based on female etiology: a tubal factor group, a polycystic ovary syndrome group, and an endometriosis group. Multiple logistic regression was used to analyze the relationship between patient characteristics and blastocyst formation. Each group of patients was divided into a training set and a validation set. The training set was used to construct the nomogram, while the validation set was used to test the performance of the model by using discrimination and calibration. The area under the curve (AUC) for the three groups indicated that the models performed fairly and that calibration was acceptable in each model.

Сondition of urogenital tract microbiotes and pro- and antioxidant system in male azoospermia

Over the past 20 years, there has been a clear trend to increase in the number of infertile men in Ukraine, their percentage reaches 50% in infertile couples. There is a significant percentage of male infertility caused by azoospermia – the lack of sperm in the ejaculate. In male infertility, azoospermia is found in 10–15% of patients, among other forms of pathospermia. Given the ambiguity of ideas about the etiology, pathogenesis and treatment and diagnostic approaches for various types of infertility, it remains important to clarify the relationship of urogenital infections with the regulatory systems of cells, including the state of the pro- and antioxidant system and the search for additional markers. 119 patients with various forms of azoospermia were examined. All patients underwent the following studies: spermogram, infectious screening, inhibin B, lipid peroxidation, activity of enzymes of the glutathione antioxidant system in sperm plasma and blood serum. Infectious screening included analysis of urethral secretions, bacteriological examination of sperm or prostate secretion, assessment of the species and quantitative composition of the microflora of the male urogenital tract. According to the results of spermogram and other diagnostic methods, a non-obstructive form of azoospermia was detected in 69 patients. In obstructive azoospermia, ejaculate as such was absent. It is suggested that inhibin B may be an important medical diagnostic test for azoospermia. As a result of the conducted researches the importance of determining the concentration of inhibin B as a marker of azoospermia was demonstrated and a negative correlation of moderate strength between the content of inhibin B and testosterone level in the plasma of men with non-obstructive azoospermia was revealed. It was found that Ureaplasma pervum and Ureaplasma urealyticum infect the male genitourinary system to the greatest extent among a number of microorganisms, both in non-obstructive and obstructive forms of azoospermia. Enterococcus faecalis is more pronounced in the sperm fluid in the non-obstructive form of azoospermia and prostate secreton in the obstructive form of azoospermia. In the non-obstructive form of azoospermia in the seminal plasma and serum, the processes of lipid peroxidation intensify, the concentration of reduced glutathione decreases and the activities of the enzymes of the glutathione antioxidant system (glutathione peroxidase and glutathione transferase) decrease. It can be considered that an important diagnostic test for the nonobstructive form of azoospermia is the ratio of reduced glutathione to oxidized glutathione in sperm plasma.

A Comparative Analysis of the Altered Levels of Human Seminal Plasma Constituents as Contributing Factors in Different Types of Male Infertility.

(1) Background: The relationships between the biochemical and immunological components in seminal plasma and their physiological effects on male reproductive system have been underreported. In this study, we evaluated the potential of several seminal plasma biochemical and immunological markers in the pathophysiological developments of the infertile male patients. The study was designed to identify and assess different markers that may be associated with semen functions in different types of male infertility. (2) Methods: A total of 50 infertile male patients who underwent checkup for fertility assessment and 50 fertile controls were included in this study. The complete medical history of each recruited participant was reviewed. The infertile sub-groups (non-obstructive azoospermia (NOA), asthenozoospermia (AS), normozoospermic infertile (NI), and oligozoospermia (OZ)) were characterized based on sperm motility and concentration, while NI patients were included after a thorough check up of their female partners as well. We investigated each sample for 21 different analytes, enzymes, trace elements, and immunological markers to find crucial markers posing as contributing factors to a specific type of male infertility. (3) Results: The levels of 15 out of 21 markers, assayed from the seminal plasma of infertile males, were significantly altered in comparison to fertile controls (p < 0.05). For the first time, microprotein levels were also analyzed. The presence of monocytes, lymphocytes, and granulocytes was limited to semen from NOA patients, while a significant increase in the level of platelets was observed in AS. Hierarchical clustering and ROC-AUC analysis identified the three most significant markers (zinc, LDH, and TG) for the healthy control group and asthenozoospermic group (AUC, of 0.92 and 0.81, respectively). (4) Conclusions: The altered levels of biochemical and immunological markers in seminal plasma might be associated with the different male infertility profiles and could be required for the sperm metabolism and maintenance. However, a larger sample size and follow up analysis is required for establishing the hypothesized panel of markers as biomarkers at clinical stage.

Clinical application of aromatase inhibitors to treat male infertility.

Infertility affects 15% of men and contributes to nearly half of all cases of infertility. Infertile men usually have impaired spermatogenesis, presenting as azoospermia or various degrees of asthenospermia and oligozoospermia. Spermatogenesis is a complex and coordinated process, which is under precise modulation by the hypothalamic-pituitary-gonadal (HPG) axis. An aberrant hormone profile, especially an imbalance between testosterone (T) and estradiol (E2), plays an essential role in male infertility. In the male, E2 is produced mainly from the conversion of T by the aromatase enzyme. Theoretically, reducing an abnormally elevated T:E2 ratio using aromatase inhibitors (AIs) could restore the balance between T and E2 and optimize the HPG axis to support spermatogenesis. For decades, AIs have been used to treat male infertility empirically. However, owing to the lack of large-scale randomized controlled studies and basic research, the treatment efficacy and safety of AIs in male infertility remain controversial. Therefore, there is a need to summarize the clinical trials and relevant basic research on the application of AIs in the treatment of male infertility. In this narrative review, we summarized the application of AIs in the treatment of male infertility, including the pharmacological mechanisms involved, clinical trials focused on patients with different types of infertility, factors affecting treatment efficacy and the side-effects. A literature search was performed using MEDLINE/PubMed and EMBASE, focusing on publications in the past four decades concerning the use of AIs for treating male infertility. The search terms included AI, male infertility, letrozole, anastrozole, testolactone, azoospermia, oligozoospermia, aromatase polymorphisms, obesity and antiestrogens, in various combinations. Clinical studies demonstrate that AIs, especially nonsteroidal letrozole and anastrozole, could significantly inhibit the production of E2 and its negative feedback on the HPG axis, resulting in increased T and FSH production as well as improved semen parameters in infertile men. Large-scale surveys suggest that obesity may result in symptoms of hypogonadism in both fertile and infertile males, such as decreased semen quality and attenuated sexual function, which can be improved by AIs treatment. Polymorphisms of the aromatase gene CYP19A1, including single nucleotide polymorphisms and tetranucleotide TTTA repeats polymorphism (TTTAn), also influence hormone profiles, semen quality and treatment efficacy of AIs in male hypogonadotropic hypogonadism and infertility. The side-effects of AIs in treating male infertility are various, but most are mild and well tolerated. The application of AIs in treating male infertility has been off-label and empirical for decades. This narrative review has summarized the target patients, dose, treatment duration and side-effects of AIs. Polymorphisms of CYP19A1 that may affect AIs treatment efficacy were also summarized, but a full understanding of the mechanisms involved in AIs action requires further study.

Peptide bioregulator amprost® in the correction of pathospermia in various types of secretory infertility

The aim of the study was to evaluate the clinical and laboratory effectiveness of the peptide bioregulator Samprost® in the correction of pathospermia in men with secretory type of infertility caused by chronic nonbacterial prostatitis (CNP) and varicocele in the postoperative period.Materials and methods. The multicenter study included 30 patients between 23 and 51 years of age: 15 patients with CNP (1st group) and 15 men with infertility due to varicocele in the postoperative period (2nd group). Patients of all groups received Samprost® for 20 days in the form of intramuscular injections of 5 mg daily. The study design provided for a traditional clinical, laboratory and specialized examination with the study of the level of antisperm antibodies, the study of sperm DNA fragmentation by the TUNEL method, the assessment of oxidative stress, a cryotolerance test, and an electron microscopic examination of the ejaculate. Statistical processing of the material was carried out using the paired Student's t test for dependent samples, and the Wilcoxon nonparametric T test was also used. The calculations were performed using the SigmaPlot 12.5 program.Results. The average age of the study participants was 36.91 ± 4.5 years (23-51 years). Among the concomitant and past diseases, the most common were patients with recurrent varicocele, May-Turner syndrome, varicose veins of the pelvis. When evaluating the effectiveness, the results of the study showed a more significant effect of the drug Samprost® in the group of patients with CNP. This concerned an increase in ejaculate volume by 11.5 %, an increase in sperm concentration by 19.4 %. Progressive sperm motility increased more in the group of patients with varicocele by 12.2 %, compared with the CNP group - 11.4 %. Similar data were obtained during cryotest.After 20-day use of the Samprost® a significant decrease in the level of free radicals in the ejaculate was noted: by 2.5 times in the group with CNP and by 2.3 in the group of patients with varicocele. Analysis of these indicators may indicate an antioxidant effect on the effect on the sperm cell, which is under serious stress in the fight against free radicals. This assumption is also confirmed by the EMIS data, which showed a positive dynamics in the number of intact heads of normal form with a normal structure of chromatin and acrosome, the number of spermatozoa with insufficiently condensed immature chromatin.Conclusion. Samprost® is an effective and safe drug for patients with secretory type of male infertility. Based on the methods of statistical analysis, including statistically significant differences in the study groups, Samprost® is more effective in patients with secretory type of male infertility in the case of CNP than in patients with varicocele in the postoperative period. More significant changes relate to the volume, concentration of sperm viability and a decrease in the level of free radicalsThe 20-day course of Samprost® increases progressive sperm motility during cryotest in patients with varicocele and CNP and can be used for substantiated preparation of patients for gamete cryopreservation and its use in preparatory assisted reproductive technologies programs using intra cytoplasmic sperm injection. A decrease in DNA fragmentation and the received electron microscopic examination of the sperm data indicate a possible influence of Samprost® on sperm morphology and require further research in this area.

Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

P–669 “Follitropin”: A retrospective, observational study comparing the efficacy of follitropin alpha biosimilar therapy in different ovarian stimulation protocols: real-world data

Abstract Study question To investigate the therapeutic efficacy of follitropin alpha biosimilar therapy in nonselected patients undergoing IVF. Summary answer This large retrospective study demonstrated similar therapeutic efficacy for follitropin alpha biosimilar therapy in women who underwent ovarian stimulation (OS) using different protocols. What is known already Based on data from the last meta-analyses (Budani et al., 2020), follitropin alpha biosimilars showed similar efficacy and safety in randomized controlled trials aimed at proving the therapeutic equivalence in terms of oocytes retrieved in women undergoing OS. In most cases, normogonadotrophic patients were enrolled in such studies without any endocrine or ovarian disturbances. The absence of real-world data can be compensated by additional post-marketing studies aimed at investigating the efficacy of biosimilars in different OS protocols using antagonists and agonists of GnRH and OS with mixed gonadotropins. Study design, size, duration A retrospective, observational, anonymized cohort study conducted at 35 IVF clinics in Russia, named “FOLLITROPIN”, compared the efficacy of OS in 2020. The OS protocols analysed where follitropin alpha biosimilar (Primapur®) was applied for at least 5 days. All of the analysed subjects underwent OS using GnRH antagonist/agonist protocols, with no restrictions on the OS protocol or food supplements/vitamins. No inclusion or exclusion criteria were applied. Overall, 5484 OS protocols were analysed. Participants/materials, setting, methods The efficacy of 5484 OS protocols was calculated, and two subgroups were extracted: (1) mixed gonadotropin OS protocols (N = 2625) vs monotherapy with Primapur® (N = 2859); (2) GnRH antagonist OS (N = 2183) vs GnRH agonist (N = 676) using only Primapur®. Demographic and clinical characteristics: (1) Age 34.9±4.8 vs 32.9±4.7 (p &amp;lt; 0.001), BMI 23.9±4.7 vs 23.6±4.5 (p &amp;lt; 0.001), IVF attempt 1.4±0.7 vs 1.3±0.6 (p &amp;lt; 0.001); (2) Age 32.9±4.6 vs 33.1±4.9 (p = 0.449), BMI 23.7±4.6 vs 23.1±4.5 (p = 0.019), and IVF attempt 1.2±0.5 vs 1.4±0.9 (p &amp;lt; 0.001). Main results and the role of chance The total efficacy of OS with Primapur®: oocytes retrieved: 9.5±7.2, MII: 6.8±6.6, 2PN: 6.1±5.8, clinical pregnancy per ET (PR) 6 weeks after ET: 38.4%. Subgroup 1 analysis: oocytes retrieved: 8.6±6.8 vs 10.3±7.4 (p &amp;lt; 0.001), MII: 6.7±6.2 vs 7.7±6.9 (p &amp;lt; 0.001), 2PN: 5.8±5.2 vs 7.2±6.2 (p &amp;lt; 0.001). There were statistically significant differences between oocyte yields in mixed vs monotherapy protocols due to subgroup differences, including age, BMI and IVF attempts. No statistically significant differences were found for PR in subgroup 1: 39.3% [95% CI: 36.9–41.7%] vs 37.6% [95% CI: 35.3–39.8%] (p = 0.314). The major accompanying gonadotropin in the mixed protocol was menotropin (75% for mixed OS protocols). Subgroup 2 analysis: oocytes retrieved: 10.5±7.5 vs 9.6±7.0 (p = 0.032), MII: 7.6±6.9 vs 6.7±5.7 (p &amp;lt; 0.001), 2PN: 7.3±6.3 vs 5.7±5.0 (p &amp;lt; 0.001). There were statistically significant differences between oocyte yields in GnRH antagonist vs GnRH agonist monotherapy due to subgroup differences, including BMI and IVF attempts. No statistically significant differences were found for PR in subgroup 2: 37.9% [95% CI: 35.5–40.5%] vs 35.9% [95% CI: 30.8–41.1%] (p = 0.482). All medicines were well tolerated at the injection site, and no serious adverse reactions were reported. This large retrospective cohort study in a nonselected population demonstrated similar clinical efficacy for follitropin alpha biosimilar therapy. Limitations, reasons for caution The real-world patient data analysed in this study were representative, showing the ability of follitropin biosimilars to develop both folliculogenesis and clinical pregnancy in a nonselected population. Additional comparative studies are needed to confirm the efficacy of the biosimilars in patients with classified types of infertility causes, including unexplained infertility. Wider implications of the findings: In this study, we demonstrated the therapeutic efficacy of biosimilars in terms of oocyte yield and clinical pregnancy development in women undergoing different OS protocols. Further large-scale studies with known hormonal levels before and during OS, as well as the micro- and macronutrient status of both parents, are needed. Trial registration number None