Sandro Esteves

• MD, PhD
• Managing Director at Androfert

In recent years, the management of male factor infertility has undergone important changes with the introduction of novel concepts, advanced testing, and therapeutic interventions. This review highlights some of these changes and discusses their impact to routine clinical practice. First, we discuss the recent changes in the World Health Organizati...

In Fertility Centers, quality should be measured by how well the organization complies with pre-defined requirements , and by how quality policies are implemented and quality objectives achieved. Having a quality management system (QMS) is a mandatory requirement for IVF centers established in most countries with regulatory guidelines, including Br...

Objective: To investigate the effectiveness of intracytoplasmic sperm injection (ICSI) using testicular sperm as a strategy to overcome infertility in men with high sperm DNA fragmentation (SDF). Design: Prospective, observational, cohort study. Setting: Private IVF centers. Patient(s): A total of 147 couples undergoing IVF-ICSI and day 3 fr...

Spermatogenesis is primarily controlled by follicle‐stimulating hormone and luteinizing hormone‐driven testosterone. Luteinizing hormone acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter‐related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins contai...

The production of spermatozoa, a process known as spermatogenesis, is primarily controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-driven testosterone. LH acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite...

Leukocytospermia, defined as ≥1×10⁶ white blood cells (WBC)/ml of semen, is a condition frequently observed in infertile men. While symptomatic leukocytospermia is often associated with genital tract infections and managed accordingly, the clinical significance of asymptomatic leukocytospermia remains uncertain-particularly in the setting of Assist...

Purpose To explore whether a 25 mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P4) levels (7–10 ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET). Methods A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients...

Purpose The purpose of this study is to investigate the impact of daily follicle-stimulating-hormone (FSH) dose on the likelihood of suboptimal response to ovarian stimulation (OS) for in vitro fertilization (IVF) according to POSEIDON’s criteria. Methods A tri-center retrospective cohort study (2015–2017) including women with normal anti-Mülleria...

Non-obstructive azoospermia (NOA) is found in up to 15% of infertile men. While several causes for NOA have been identified, the exact etiology remains unknown in many patients. Advances in assisted reproductive technology, including intracytoplasmic sperm injection (ICSI) and testicular sperm retrieval, have provided hope for these patients. This...

Study question What factors are associated with sperm retrieval (SR) success through microdissection testicular sperm extraction (micro-TESE) in nonobstructive azoospermic (NOA) males with biochemical hypogonadism? Summary answer The SR success in hypogonadal NOA males is associated with FSH levels, pre-micro-TESE hormonal stimulation, presence of...

Background Existing literature does not provide accurate epidemiological data regarding the true prevalence of men with non‐obstructive azoospermia (NOA) who would be eligible for hormonal optimization therapy, according to specific pre‐treatment criteria. Objectives To investigate the characteristics of those men with NOA who would qualify for th...

Objective This review provides a comprehensive overview of the existing research on the seminal microbiome and its association with male infertility, while also highlighting areas that warrant further investigation. Methods A narrative review was conducted, encompassing all relevant studies published between 1980-2023 on the male reproductive trac...

Purpose To determine the risk of not being a poor responder in ovarian stimulation (OS) for in vitro fertilization (IVF) when ovarian reserve markers are discordant—one falling within Poseidon’s criteria normal range (e.g., anti-Müllerian hormone (AMH) ≥ 1.2 ng/mL or antral follicle count (AFC) ≥ 5), and the other in the poor ovarian reserve range....

Approximately one in twenty men have sperm counts low enough to impair fertility but little progress has been made in answering fundamental questions in andrology or in developing new diagnostic tools or management strategies in infertile men. Many of these problems increase with age, leading to a growing population of men seeking help. To address...

Objective To investigate the prevalence and clinical implications of biochemical hypogonadism in infertile men with nonobstructive azoospermia (NOA). Design Cohort study. Setting University-affiliated tertiary center for male reproductive health. Patients 767 consecutive normogonadotropic or hypergonadotropic patients with NOA undergoing inferti...

The purpose of this article is to provide an explanation of the background behind a checklist that declares the laboratory methods used in a scientific study. It focuses primarily on implementing laboratory procedures to yield reliable results in basic semen examinations. While the World Health Organization (WHO) and international standards provide...

Background: In a true-natural cycle (t-NC), optimal progesterone (P4) output from the corpus luteum is crucial for establishing and maintaining an intrauterine pregnancy. In a previous retrospective study, low P4 levels (< 10 ng/mL) measured one day before warmed blastocyst transfer in t-NC were associated with significantly lower live-birth rates...

To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori,...

Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic ex...

Study question Is there an association between follicular phase endocrine and ultrasonographic characteristics and ongoing pregnancy rates (OPRs) in true-natural cycle (t-NC) frozen embryo transfers (FETs)? Summary answer Endometrial thickness one day before ovulation is the only independent predictor of ongoing pregnancy (OP) in t-NC FET cycles....

Study question Are ongoing pregnancy rates (OPRs) similar between subcutaneous (sc) progesterone (P) and vaginal P administration in hormone replacement therapy (HRT) frozen embryo transfer (FET) cycles? Summary answer The OPRs were similar between sc and vaginal P administration; however, 15.8% of patients in the vaginal group needed additional P...

Study question Unlike previous reviews, our meta-analysis investigated protocols involving only women with diminished ovarian reserve (DOR) identified by antral follicle count and/or AMH (POSEIDON criteria). Summary answer Testosterone, GH and delayed antagonist starting protocol are associated with better IVF outcomes comparing with respective co...

Research question: Does administration of subcutaneous (s.c.) progesterone support ongoing pregnancy rates (OPR) similar to vaginal progesterone using a rescue protocol in hormone replacement therapy frozen embryo transfer cycles? Design: Retrospective cohort study. Two sequential cohorts - vaginal progesterone gel (December 2019-October 2021; n...

Background: Total fertilization failure (TFF) is the failure of all metaphase II oocytes to fertilize in ART cycles. The phenomenon represents a known cause of infertility, affecting 1-3% of ICSI cycles. Oocyte activation deficiency (OAD) is the leading cause of fertilization failure, attributed to sperm- or oocyte-related issues, although until r...

Purpose To provide an agreed upon definition of hyper-response for women undergoing ovarian stimulation (OS)? Methods A literature search was performed regarding hyper-response to ovarian stimulation for assisted reproductive technology. A scientific committee consisting of 5 experts discussed, amended, and selected the final statements in the que...

Human papillomavirus (HPV) is a common sexually transmitted disease that has been linked to both cancer and reproductive health issues. While its impact on fertility and pregnancy success has been studied, there is still too little evidence about the influence of HPV on assisted reproductive technology (ART). Therefore, there exists a need for HPV...

STUDY QUESTION Do early- and mid-luteal serum progesterone (P4) levels impact ongoing pregnancy rates (OPRs) in fresh blastocyst transfer cycles using standard luteal phase support (LPS)? SUMMARY ANSWER A drop in serum P4 level from oocyte pick-up (OPU) + 3 days to OPU + 5 days (negative ΔP4) is associated with a ∼2-fold decrease in OPRs. WHAT IS...

A high ovarian response to conventional ovarian stimulation (OS) is characterized by an increased number of follicles and/or oocytes compared with a normal response (10-15 oocytes retrieved). According to current definitions, a high response can be diagnosed before oocyte pick-up when >18-20 follicles ≥11-12 mm are observed on the day of ovulation...

Gonadotropin therapy to treat specific male infertility disorders associated with hypogonadotropic hypogonadism is evidence-based and effective in restoring spermatogenesis and fertility. In contrast, its use to improve fertility in men with idiopathic oligozoospermia or nonobstructive azoospermia remains controversial, despite being widely practic...

The aim of this study was to assess mitochondrial DNA analysis as a predictor of the pregnancy potential of biopsied preimplantation embryos. The study included 78 blastomeres biopsied from day 4 cleavage stage euploid embryos. The embryo karyotype was confirmed by 24-chromosome preimplantation genetic testing for aneuploidies using the Illumina Ne...

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination a...

Study question Does timing of WBT in t-NC differ according to six different commonly definitions for LH surge, and if so, do differences in timing impact OPRs? Summary answer Performing WBT on follicular collapse+5 days is equivalent to LH surge +7/+8 /+9 days in terms of OPRs, using six different definitions of LH surge. What is known already Pi...

Study question Does the ongoing pregnancy rate (OPR) of HRT with or without GnRH-agonist suppression and t-NC protocols differ in patients undergoing warmed blastocyst transfer? Summary answer HRT, with or without GnRH-agonist suppression, and t-NC protocols are associated with comparable OPRs in patients undergoing warmed blastocyst transfer. Wh...

Purpose Nonobstructive azoospermia (NOA) associated with primary spermatogenic failure is a common cause of male infertility usually considered untreatable; however, some reports have suggested that hormonal stimulation to boost the intra-testicular testosterone level and spermatogenesis might increase the chance of achieving pregnancy using homolo...

Research Question Does the timing of warmed blastocyst transfer in true natural cycle (t-NC) differ according to six different commonly used definitions of luteinizing hormone (LH) surge, and do differences in timing have any impact on ongoing pregnancy rate (OPR)? Design Prospective monitoring, including repeated blood sampling and ultrasound ana...

The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria identify and classify the so-called ‘low-prognosis’ patients undergoing assisted reproductive technology (ART). Recent large-scale studies using real-world data (RWD) have shown that patients classified under this system have distinct reproductive outcomes...

Since the birth of Louise Brown in 1978 via IVF, reproductive specialists have acquired enormous knowledge and refined several procedures, which are nowadays applied in assisted reproductive technology (ART). One of the most critical steps in this practice is the fertilization process. In the early days of IVF, a remarkable concern was the unpleasa...

Purpose Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromo...

Increasing evidence has demonstrated that obesity impairs female fertility and negatively affects human reproductive outcome following medically assisted reproduction (MAR) treatment. In the United States, 36.5% of women of reproductive age are obese. Obesity results not only in metabolic disorders including type II diabetes and cardiovascular dise...

Background: Efficient and safe embryo vitrification techniques have contributed to a marked worldwide increase in the use of elective frozen embryo transfer (FET). Pinpointing the day of ovulation, more commonly by documentation of the LH surge and less commonly by ultrasonography, is crucial for timing of FET in a true natural cycle (t-NC) to max...

Purpose: Nonobstructive azoospermia (NOA) associated with primary spermatogenic failure is a common cause of male infertility usually considered untreatable; however, some reports have suggested that hormonal stimulation to boost the intra-testicular testosterone level and spermatogenesis might increase the chance of achieving pregnancy using homo...

Infections may act with variable impact on the physiopathology of the reproductive organs, determining infertility or reducing the outcomes of assisted reproduction technology. The aim of this narrative review is to describe the existing evidence regarding the pathogens with a supposed or recognized role in reproductive medicine. Viral hepatitis, a...

Purpose: Sperm DNA fragmentation (SDF) and seminal oxidative stress are emerging measurable factors in male factor infertility, which interventions could potentially reduce. We evaluated (i) the impact of lifestyle changes combined with oral antioxidant intake on sperm DNA fragmentation index (DFI) and static oxidation-reduction potential (sORP),...

Objective: To investigate the intraindividual agreement of the sperm chromatin dispersion (SCD) assay results to assess sperm DNA fragmentation (SDF) in men with infertility. Design: Diagnostic test reliability study. Setting: Andrology laboratories. Patient(s): A total of 219 men with infertility. Intervention(s): Sperm DNA fragmentation...

PurposeNonobstructive azoospermia (NOA) is associated with intrinsic testicular defects that severely impair sperm production. Although NOA invariably leads to infertility, focal sperm production may exist in the testicles of affected patients, which can be retrieved and used for intracytoplasmic sperm injection (ICSI) to generate healthy offspring...

In the last decades, the universal use of mobile phones has contributed to radiofrequency electromagnetic radiation environmental pollution. The steady growth in mobile phone usage has raised concerns about the effects of phone radiation on male reproductive health. Epidemiological studies report a sharp decline in sperm counts in developing countr...

Study question Is mitochondrial DNA viability ratio of day–4 biopsied embryos associated with embryo implantation potential? Summary answer The mitochondrial DNA viability ratio is significantly higher in embryos that implant. The score might help to select euploid embryos for single embryo transfer. What is known already Embryo euploidy is a cri...

Despite the worldwide increase in frozen embryo transfer, the search for the best protocol to prime endometrium continues. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required. Currently, low-quality evidence indicates that, natural cycle...

Purpose: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. Materials and methods: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the...

Mitochondoiral vlaues as a tool to monitor embryo implantation power

Abstract Introduction Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assist...

The development of surgical sperm retrieval procedures can be considered as the single most important breakthrough in the field of male infertility. Various testicular sperm retrieval procedures exist and are indicated in patients with obstructive and nonobstructive azoospermia, as well as patients with high levels of sperm DNA fragmentation and se...

Background A Delphi consensus was conducted to evaluate global expert opinions on key aspects of assisted reproductive technology (ART) treatment. Methods Ten experts plus the Scientific Coordinator discussed and amended statements plus supporting references proposed by the Scientific Coordinator. The statements were distributed via an online surv...

Objective To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Infertile men with clinical varicocele subjected to varicocelectomy. Intervention(s) Systematic search using PubMed...

Obtaining good quality sperm for in-vitro fertilization, ICSI, or for cryopreservation can be a major problem if a man suffers from medical conditions that preclude normal collection. Major advances in sperm retrieval and preparation techniques have been witnessed in recent years, allowing a better understanding of the contribution of the sperm to...

Obtaining good quality sperm for in-vitro fertilization, ICSI, or for cryopreservation can be a major problem if a man suffers from medical conditions that preclude normal collection. Major advances in sperm retrieval and preparation techniques have been witnessed in recent years, allowing a better understanding of the contribution of the sperm to...

The aim of this paper was to estimate the effect of dexamethasone during ovarian stimulation in women of different reproductive age with elevated early follicular phase progesterone level undergoing fresh IVF cycle. This study is a prospective longitudinal analysis of consecutive women who underwent fresh IVF cycles at a single center, between Janu...

Study question: What is the agreement between antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels when used to patient classification according to the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria? Summary answer: Our study indicates a strong agreement between the AFC and the AMH levels...

The POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria were developed to help clinicians identify and classify low-prognosis patients undergoing assisted reproductive technology (ART) and provide guidance for possible therapeutic strategies to overcome infertility. Since its introduction, the number of publish...

Objective To estimate the prevalence of low-prognosis patients according to the POSEIDON criteria using real-world data. Design Multicenter population-based cohort study. Settings Fertility clinics in Brazil, Turkey, and Vietnam. Patients Infertile women undergoing assisted reproductive technology using standard ovarian stimulation with exogenou...

The scope of the clinical embryology laboratory has expanded over recent years. It now includes conventional in vitro fertilization (IVF) techniques and complex and timedemanding procedures like blastocyst culture, processing of surgically retrieved sperm, and trophectoderm biopsy for preimplantation genetic testing. These procedures require a stab...

The scope of the clinical embryology laboratory has expanded over recent years. It now includes conventional in vitro fertilization (IVF) techniques and complex and time-demanding procedures like blastocyst culture, processing of surgically retrieved sperm, and trophectoderm biopsy for preimplantation genetic testing. These procedures require a sta...

The prolonged lockdown of health facilities providing non‐urgent gamete cryopreservation –as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS‐CoV‐2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and pr...

Abstract The prolonged lockdown of health services providing high-complexity fertility treatments –as currently recommended by many reproductive medicine entities– is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive techn...

COVID-19 is the world's most massive epidemic known to date. In order to prevent hospital burdens, governments around the world have adopted restrictive containment measures. Such measures have led to a temporary suspension of all non-urgent clinical procedures. With the reduction of con-tagions, in some country there is a slow and gradual restorat...

Poor ovarian response remains one of the most challenging tasks for an IVF clinician. In this review, we aim to highlight the ongoing research for optimizing the prognosis in poor ovarian response patients. The newly introduced POSEIDON criteria argue that the first step is to move from a poor response to a poor prognosis concept, while improving i...

Intracytoplasmic sperm injection (ICSI), combined with surgical sperm retrieval (SR) techniques, is the sole option for patients with non-obstructive azoospermia to achieve fertility; however, with suboptimal results. Given the variability in clinical presentation, the potential role of factors that can predict the likelihood of successful testicul...

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the disease so-called COVID-19, represents the most exceptional health, social, economic, and humanitarian crisis known to humankind since the H1N1 flu of 1918. So far, it affected 213 countries, infecting over 100,000 people daily worldwide, wi...

We herein summarise the evidence concerning the impact of sperm DNA fragmentation in various clinical infertility scenarios and the advances on sperm DNA fragmentation tests. The collected evidence was used to formulate 41 recommendations. Of these, 13 recommendations concern technical aspects of sperm DNA fragmentation testing, including pre-analy...

Clinical implications of sperm DNA frgmentation tetsing

Objective To explore predictors of successful sperm retrieval (SR) and to identify potentially suitable candidates for testicular sperm aspiration (TESA), a more straightforward, less traumatic, and less costly procedure than open surgical SR methods. Design Retrospective chart review. Setting Academic tertiary medical center. Patients A total o...

Background: The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, named coronavirus disease 19 (COVID-19), is not the first well-known spillover of an animal originated virus to infect humans. However, one of the few to make such a fast jump in a powerful evolutionary shortcut. The incredible pattern of ag...

Purpose: To report the utilization of diagnostic intracytoplasmic sperm injection (D-ICSI), an ICSI cycle performed in the natural cycle, to obtain information about embryo development potential after sperm injection into zona pellucida (ZP)-free oocytes. Materials and Methods: We report the case of a couple with primary unexplained infertility wi...