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Updates in Diagnosis and Treatment of Infertility

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Reproductive Medicine & Andrology".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 28184

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Special Issue Editors

Prof. Dr. Jacek Szamatowicz

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Guest Editor

Head of the Department of Gynecology and Gynecological Oncology, Medical University, Bialystok, Poland
Interests: infertility; endometriosis; surgical treatment of infertility; assisted reproduction techniques

Prof. Dr. Sławomir Wołczyński

E-Mail Website
Co-Guest Editor

Head of the Department of Reproduction and Gynecological Endocrinology, Medical University Bialystok, Bialystok, Poland
Interests: assisted reproduction techniques; induction of ovulation; ovulatory disorders

Special Issue Information

Dear Colleagues,

Infertility means a lower capacity to conceive compared to the general population. The most common definition is that provided by the World Health Organization: a failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. It should always be considered as a problem for the couple, not a single patient. Infertility is a frustrating condition for both partners, who can be categorized into two groups: those who will require therapy and those who are subfertile but may conceive without therapy. Infertility and subfertility affect a significant part of population There are several factors in infertility, the most important being ovulatory disorders, endometriosis and adenomyosis, tubal and uterine factors and male infertility. The diagnosis and treatment of infertility are very problematic, and there are no complete medical solutions to this problem The literature shows many publications on this subject, with many proposals of diagnostic and treatment algorithms. However, there is no single procedure that undoubtedly leads to pregnancy and the birth of a healthy baby, and we operate with so-called statistical approximation regarding the chance of pregnancy. Generally, all treatments for infertility are characterized by 25–35% rates of success according to the “baby taken home” parameter, which means that the failure rate is up to 75%. This creates enormous stress for the couples, who face huge financial and emotional costs for the procedures. Can we bring more happiness to these couples? Are there new treatment options with more predictable outcomes that would save unfortunate patients from bearing the heavy burden of procedures when they have no chance of success? I hope that this Special Issue will bring answers to many questions surrounding this devastating disease.

Prof. Dr. Jacek Szamatowicz
Prof. Dr. Sławomir Wołczyński
Guest Editors

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Keywords

Infertility
Diagnostic tests
Treatment
Endometriosis
Myomas
Tubal factor
Male factor of infertility
Assisted reproduction techniques

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Published Papers (9 papers)

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Research

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16 pages, 2913 KiB

Open AccessArticle

Functional Implications of Estrogen and Progesterone Receptors Expression in Adenomyosis, Potential Targets for Endocrinological Therapy

by Maria Sztachelska, Donata Ponikwicka-Tyszko, Lydia Martínez-Rodrigo, Piotr Bernaczyk, Ewelina Palak, Weronika Półchłopek, Tomasz Bielawski and Sławomir Wołczyński

J. Clin. Med. 2022, 11(15), 4407; https://doi.org/10.3390/jcm11154407 - 28 Jul 2022

Cited by 9 | Viewed by 2714

Abstract

Adenomyosis is a common gynaecological disease associated with the presence of endometrial lesions in the uterine myometrium. Estrogens have been proven to be the crucial hormones driving the growth of adenomyosis. Little is known about the distinct mechanisms of progesterone action in adenomyosis. Hence, in this study, we decided to characterize the expression of all nuclear and membrane estrogen and progesterone receptors. Additionally, as a functional investigation, we monitored prolactin production and cell proliferation after estradiol and progesterone treatments. We confirmed the presence of all nuclear and membrane estrogen and progesterone receptors in adenomyotic lesions at gene and protein levels. The expression of membrane progesterone receptors α and β (mPRα, mPRβ) as well as estrogen receptor β (ERβ) was upregulated in adenomyosis compared to normal myometrium. Estradiol significantly increased adenomyotic cell proliferation. Progesterone and cAMP upregulated prolactin secretion in adenomyosis in the same pattern as in the normal endometrium. In the present study, we showed the functional link between estradiol action and adenomyotic cell proliferation, as well as progesterone and prolactin production. Our findings provide novel insights into the sex steroid receptor expression pattern and potential regulated pathways in adenomyosis, suggesting that all receptors play an important role in adenomyosis pathophysiology. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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19 pages, 8032 KiB

Open AccessArticle

Ameliorative Sexual Behavior and Phosphodiesterase-5 Inhibitory Effects of Spondias mangifera Fruit Extract in Rodents: In Silico, In Vitro, and In Vivo Study

by Mohammad Khalid, Mohammed H. Alqarni, Shadma Wahab, Sivakumar Annadurai, Mubarak A. Alamri, Ahmed I. Foudah, Tariq M. Aljarba, Juber Akhtar, Badruddeen and Sarfaraz Ahmad

J. Clin. Med. 2022, 11(13), 3732; https://doi.org/10.3390/jcm11133732 - 28 Jun 2022

Cited by 11 | Viewed by 2726

Abstract

The ethanolic extracts of Spondias mangifera fruit (SMFE) were evaluated for aphrodisiac activity. The in-vitro phosphodiesterase-5 (PDE-5) inhibition was assessed based on in-silico molecular docking and simulation studies. In addition, the in-vivo sexual behavior was analyzed in the form of mount (MF, ML), intromission (IF, IL), and ejaculation (EF, EL) frequencies and latencies to validate the in-vitro results. Some biochemical parameters, including PDE-5, nitric oxide, and testosterone, were also observed. The above extract constituted β-amyrin, β-sitosterol, and oleanolic acid and showed tremendous binding with phosphodiesterase-5 and sildenafil. Both the sildenafil and ethanolic extracts (200 and 400 mg/kg/d bodyweight) significantly (p < 0.1, p < 0.05) increased MF, IF, and EF, respectively. In contrast, ML and IL significantly (p < 0.1) decreased, and EL significantly (p < 0.1) increased compared with a normal group of animals. The ethanolic extracts (200 and 400 mg/kg/d bodyweight) and sildenafil further significantly (p < 0.05, p < 0.1) diminished PDE-5 activity significantly (p < 0.05, p < 0.1) and enhanced nitric oxide and testosterone levels, as compared with normal rodents. Therefore, the S. mangifera ethanolic extract might be a valuable alternate aphrodisiac for erectile dysfunction. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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12 pages, 1062 KiB

Open AccessArticle

Marking the Profile of the Microflora of the Endometrium and Uterine Cervix in Women as a Potential Factor Determining the Effectiveness of In Vitro Fertilization

by Anna Bednarska-Czerwińska, Michał Czerwiński, Emilia Morawiec, Aleksandra Łach, Anna Ziaja, Adrian Kusaj, Patrycja Strączyńska, Dorota Sagan, Dariusz Boroń and Beniamin Oskar Grabarek

J. Clin. Med. 2022, 11(12), 3348; https://doi.org/10.3390/jcm11123348 - 10 Jun 2022

Cited by 7 | Viewed by 3154

Abstract

One promising research trend involves evaluating the influence of microbiota in the reproductive system of women on becoming pregnant and maintaining pregnancy. The goal of this study was to define the microflora profile of the endometrium and uterine cervix in women qualified for an in vitro fertilization (IVF) procedure, which is expected to contribute to increasing the percentage of successful IVF implantations. Based on the conducted molecular analysis in the collected swabs, 22 bacterial strains were identified. Eleven strains (57%) that were isolated belong to the physiological microflora, the most common strain of which was Lactobacillus. Eight of the isolated strains (33%) were pathological microflora, among which the most common bacteria were from the Enterobacteriaceae family (which includes E. coli, Shigella, and Salmonella). Finally, three of the bacterial strains (10%) may be a component of both physiological or pathological microflora of the vagina: Bifidobacterium breve, Bifidobacterium longum group, and Alloscardovia omnicolens. The presence of Escherichia coli was detected in six women, Staphylococcus aureus also in six patients, Atopobium parvulum in three, Streptococcus salivarius group in three, Enterococcus faecalis in four, and Aerococcus christensenii in two patients. We found statistically significant relationships (p < 0.05) between Lactobacillus fermentum and Enterococcus faecalis, Lactobacillus delbrueckii and Escherichia coli groups, Lactobacillus FN667084_s and Staphylococcus aureus groups, as well as Lactobacillus fermentum and Streptococcus agalactiae. Based on the conducted study, it may be confirmed that the endometrium is, to a large extent, colonized by lactic acid bacilli. Apart from that, endometrial dysbiosis was not noted in patients qualified for the IVF procedure. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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12 pages, 1040 KiB

Open AccessArticle

Spermatic Microbiome Characteristics in Infertile Patients: Impact on Sperm Count, Mobility, and Morphology

by Clémence Gachet, Manon Prat, Christophe Burucoa, Philippe Grivard and Maxime Pichon

J. Clin. Med. 2022, 11(6), 1505; https://doi.org/10.3390/jcm11061505 - 9 Mar 2022

Cited by 12 | Viewed by 2817

Abstract

Through sperm alteration, semen microbiota tend to be recognized as a cause of infertility, but due to the limited number of studies focusing on this ecological niche, this hypothesis remains controversial. This study aimed to characterize and compare the bacterial communities of sperm samples from patients undergoing couple infertility treatment at the time of diagnosis. The study was prospective (September 2019 to March 2020), monocentric, and focused on alterations of spermatic parameters: count, motility, and morphology. After the amplification of the 16S rDNA (V1 to V3), libraries (n = 91, including 53 patients with abnormalities) were sequenced using the MiSeq platform (Illumina). After quality control processing using a homemade pipeline (QIIME2 modules), the main genera were: Prevotella, Finegoldia, Pseudomonas, Peptinophilus, Streptococcus, Anaerococcus and Corynebacterium. Restricted diversity was observed in samples from patients with abnormal sperm morphology (α-diversity, p < 0.05), whereas diversity increased in patients with an abnormal sperm count (β-diversity, p < 0.05). The enrichment of the genus Prevotella and Haemophilus was observed in negative sperm culture samples and samples with abnormal counts, respectively (p < 0.05). Microbiota differed in their composition according to sperm parameters. Finally, this work highlights the need for the optimization of the management of couples undergoing infertility treatment, possibly by modulating the genital microbiome. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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22 pages, 6506 KiB

Open AccessArticle

Cellular Processes in Human Ovarian Follicles Are Regulated by Expression Profile of New Gene Markers—Clinical Approach

by Błażej Chermuła, Wiesława Kranc, Piotr Celichowski, Bogusława Stelmach, Hanna Piotrowska-Kempisty, Paul Mozdziak, Leszek Pawelczyk, Robert Zygmunt Spaczyński and Bartosz Kempisty

J. Clin. Med. 2022, 11(1), 73; https://doi.org/10.3390/jcm11010073 - 24 Dec 2021

Cited by 1 | Viewed by 2762

Abstract

In the growing ovarian follicle, the maturing oocyte is accompanied by cumulus (CCs) and granulosa (GCs) cells. Currently, there remain many unanswered questions about the epithelial origin of these cells. Global and targeted gene transcript levels were assessed on 1, 7, 15, 30 days of culture for CCs and GCs. Detailed analysis of the genes belonging to epithelial cell-associated ontological groups allowed us to assess a total of 168 genes expressed in CCs (97 genes) and GCs (71 genes) during long-term in vitro culture. Expression changes of the analyzed genes allowed the identification of the group of genes: TGFBR3, PTGS2, PRKX, AHI1, and IL11, whose expression decreased the most and the group of ANXA3, DKK1, CCND1, STC1, CAV1, and SFRP4 genes, whose expression significantly increased. These genes’ expression indicates CCs and GCs epithelialization processes and their epithelial origin. Expression change analysis of genes involved in epithelization processes in GCs and CCs during their in vitro culture made it possible to describe the most significantly altered of the 11 genes. Detailed analysis of gene expression in these two cell populations at different time intervals confirms their ovarian surface epithelial origin. Furthermore, some gene expression profiles appear to have tumorigenic properties, suggesting that granulosa cells may play a role in cancerogenesis. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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11 pages, 7072 KiB

Open AccessArticle

The Association between Bisphenol A, Steroid Hormones, and Selected MicroRNAs Levels in Seminal Plasma of Men with Infertility

by Ewelina Palak, Weronika Lebiedzińska, Sławomir Anisimowicz, Maria Sztachelska, Piotr Pierzyński, Wiesław Wiczkowski, Beata Żelazowska-Rutkowska, Gabriella Nicole Niklińska, Donata Ponikwicka-Tyszko and Sławomir Wołczyński

J. Clin. Med. 2021, 10(24), 5945; https://doi.org/10.3390/jcm10245945 - 18 Dec 2021

Cited by 17 | Viewed by 2832

Abstract

Bisphenol A (BPA), the most common endocrine-disrupting chemical, has been associated with male reproductive dysfunctions. Recently, it has been shown that BPA may also affect miRNAs expression. Herein, we aimed to evaluate the association of BPA levels with steroid hormone concentration and circulating miRNAs levels to investigate the potential direct effect of BPA on homeostasis in the testis environment. The level of BPA in the seminal plasma of azoospermic men was significantly higher compared to the healthy control. The concentrations of estradiol (E2) and androstenedione (A) were significantly decreased in the seminal plasma of azoospermic men compared to the normospermic men. The levels of miR-let-7a, miR-let-7b, and miR-let-7c were significantly up-regulated, and the level of miR-518f was significantly down-regulated in the seminal plasma of the azoospermic men compared to the healthy control. The level of BPA correlated negatively with sperm concentration and normal semen morphology. A significant positive correlation was found between BPA levels and miR-let-7a and miR-let-7c levels, whereas BPA negatively correlated with miR-518f levels. Our results suggest that BPA may negatively affect sperm quality. Moreover, BPA correlated with the miR-let-7a, miR-let-7c, and miR-518f levels in seminal plasma, which suggests that BPA may act directly in seminal plasma, affecting the testicular environment. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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17 pages, 1980 KiB

Open AccessArticle

Impact of the Vaginal and Endometrial Microbiome Pattern on Assisted Reproduction Outcomes

by María del Carmen Diaz-Martínez, Andrea Bernabeu, Belén Lledó, Concepción Carratalá-Munuera, Jose A. Quesada, Francisca M. Lozano, Vicente Ruiz, Ruth Morales, Joaquín Llácer, Jorge Ten, Juan Carlos Castillo, Adoración Rodríguez, Rauf Nouni-García, Adriana López-Pineda, Belén Moliner and Rafael Bernabeu

J. Clin. Med. 2021, 10(18), 4063; https://doi.org/10.3390/jcm10184063 - 8 Sep 2021

Cited by 40 | Viewed by 3750

Abstract

Uterine microbiota may be involved in reproductive health and disease. This study aims to describe and compare the vaginal and endometrial microbiome patterns between women who became pregnant and women who did not after in vitro fertilization. We also compared the vaginal and endometrial microbiome patterns between women with and without a history of repeated implantation failures (RIF). This pilot prospective cohort study included 48 women presenting to the fertility clinic for IVF from May 2017 to May 2019. Women who achieved clinical pregnancy presented a greater relative abundance of Lactobacillus spp. in their vaginal samples than those who did not (97.69% versus 94.63%; p = 0.027. The alpha and beta diversity of vaginal and endometrial samples were not statistically different between pregnant and non-pregnant women. The Faith alpha diversity index in vaginal samples was lower in women with RIF than those without RIF (p = 0.027). The alpha diversity of the endometrial microbiome was significantly higher in women without RIF (p = 0.021). There were no significant differences in the vaginal and endometrial microbiomes between pregnant and non-pregnant women. The relative abundance of the genera in women with RIF was different from those without RIF. Statistically significant differences in the endometrial microbiome were found between women with and without RIF. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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Review

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11 pages, 2171 KiB

Open AccessReview

Is There Still a Place for Reconstructive Surgery in Distal Tubal Disease?

by Bogdan Obrzut and Marzanna Obrzut

J. Clin. Med. 2022, 11(12), 3278; https://doi.org/10.3390/jcm11123278 - 8 Jun 2022

Cited by 4 | Viewed by 2901

Abstract

Tubal diseases account for 25–40% of female factor infertility. Mainly, they involve the distal part of the fallopian tube, and hydrosalpinx is the most severe manifestation. Usually, the management decision is made between reconstructive surgery and ART, depending on the severity of the tubal damage, patient age, ovarian reserve, and seminogram, as well as financial, religious, ethical, and psychological factors. Estimated live-birth rates after corrective surgery range from 9% to 69%. The success rate of IVF is about 30% live-birth rate per cycle initiated in women across all ages with tubal factor infertility. Surgery offers a long-term cure and patients may attempt conception many times but are burdened with perioperative adverse events. IVF bypasses potential complications of operative treatment; however, this has its own unique risks. The effectiveness of reconstructive surgery versus ART has not been adequately evaluated. The success of fertility management depends on a thorough interpretation of existing data and careful patient selection. The presented review provides updates on the most recent progress in this area. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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12 pages, 957 KiB

Open AccessReview

Different Strategies of Preimplantation Genetic Testing for Aneuploidies in Women of Advanced Maternal Age: A Systematic Review and Meta-Analysis

by Wei-Hui Shi, Zi-Ru Jiang, Zhi-Yang Zhou, Mu-Jin Ye, Ning-Xin Qin, He-Feng Huang, Song-Chang Chen and Chen-Ming Xu

J. Clin. Med. 2021, 10(17), 3895; https://doi.org/10.3390/jcm10173895 - 30 Aug 2021

Cited by 14 | Viewed by 3387

Abstract

Background: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. Method: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). Results: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03–1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04–1.79). Conclusion: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy. Full article

(This article belongs to the Special Issue Updates in Diagnosis and Treatment of Infertility)

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