This manuscript reviews sperm morphology and its disorders in the context of infertility. A new look into an old challenge is delivered, based on contemporary scientific and clinical evidence. We highlight the functional repercussions of sperm morphology aberrations and dissect the cause and effect of a variety of insults and pathogenic mechanisms focusing on the relationships among sperm shape, function, and compartmental analysis of cellular and subcellular structures. Different types of teratozoospermia are identified as a sequela of aberrant spermiogenesis, and their proven or speculated origins are discussed. In addition to known and suspected genetic causes, oxidative damage is highlighted as a major plausible pathogenic factor. The examination of sperm morphology with the use of strict criteria provides valuable information to guide the clinician to direct therapeutic management. We emphasize that sperm morphology is probably the most relevant parameter of the traditional semen evaluation and can be used as a valid biomarker of functional deficiencies, providing information about chances of conception. The information provided by the examination of sperm morphology as part of a complete semen analysis becomes more and more significant from a clinical point of view for infertility and perhaps men's health. (Fertil Steril Rev (R) 2021;2:75-92. (c) 2020 by American Society for Reproductive Medicine.)

In patients with acceptable sperm count and motility, two patterns of abnormal morphology, judged with strict criteria, were identified and described. Patients with <4% normal forms and <30% morphology index (summation of normal and slightly amorphous forms) had a fertilization rate of 7.6% of the oocytes (P pattern, poor prognosis). Patients with normal morphology between 4 and 14% had a significantly better fertilization rate of 63.9% of the oocytes (P < 0.0001). Cases with >14% normal forms fertilized within the normal range for the laboratory. By evaluating sperm morphology with the proposed strict criteria, its predictive value in in vitro fertilization is enhanced.

Background: Clinical ultrasound is commonly used in medical practices worldwide due to the multiple benefits the modality offers clinicians. Rigorous credentialing standards are necessary to safeguard patients against operator errors. The purpose of the study was to establish and analyse the barriers that specifically lead to poor credentialing success within a resource-limited clinical ultrasound training programme. Methods: An electronic cross-sectional survey was e-mailed to all trainees who attended the introductory clinical ultrasound courses held in Cape Town since its inception in 2009 to 2013. All trainees were followed until they completed their training programme in 2015. Results: Only one fifth of trainees (n = 43, 19.7%), who entered the Cape Town training programme, credentialed successfully. Ninety (n = 90, 41.3%) trainees responded to the survey. Eighty-six (n = 86) surveys were included for analysis. Time constraints were the highest ranked barrier amongst all trainees. Access barriers (to trainers and ultrasound machines) were the second highest ranked amongst the non-credentialed group. A combination between access and logistical barriers (e.g. difficulty in finding patients with pathology to scan) were the second highest ranked in the credentialed group. Conclusions: Access barriers conspire to burden the Cape Town clinical ultrasound training programme. Novel solutions are necessary to overcome these access barriers to improve future credentialing success.

Objective: To determine whether the use of prolonged, 8 days course of clomiphene citrate (CC) versus the standard use of 5 days is an effective method to prevent premature luteinizing hormone (LH) surge in assisted reproductive technology (ART) program. Materials and Methods: Eligible participants were randomized into one of the two treatment groups, In Group A, the patients received CC 100 mg for 5 days from cycle day 3-7 plus human menopausal gonadotropin (hMG), 150-225 IU on alternate days. In Group B, patients received CC 100 mg for 8 days from cycle day 3-10 plus hMG. Cycles were monitored with ultrasound and urinary LH tests only. Results: Two hundred and thirty-eight patients were randomized, but a total of 227 were analyzed. The percentage risk of premature LH surge was similar in both groups with (20% Group A vs. 24% Group B, P = 0.6) and there was no significant difference in live birth and clinical pregnancy rates per initiated cycle between the two groups, 6.4% Group A versus 10.6% in Group B and 12% (a) versus 17% (b), respectively. Cycle cancellation rates were also similar between the two groups, 36% (a) versus 31% (b). Conclusion: The trial shows that prolonged, 8 days course of CC does not suppress premature LH surge in ART program.

Varicocele is present in approximately 15% of men, and, although it is the most commonly diagnosed cause of male infertility, nearly two-thirds of men with varicoceles remain fertile. It was decided to make use of the current evidence obtained from the previous meta-analyses between 2004 and 2015 as well as available articles covering this field, preferably randomized controlled articles dealing with the topic of semen analysis before and after repair. Two important meta-analyses were discussed as well as other articles dealing with the topic of semen analysis before and after varicocelectomy. The evidence suggests that all semen parameters improve after varicocele repair. Based on the available evidence, it is clear that there is a benefit in treating men with a palpable varicocele. One can expect that all semen parameters will improve within 3 months after repair.

Objective: To evaluate PPI as a strategy to make ART affordable.

This article outlines the trial model in reproductive medicine that was created as a first step in the development of a business model for medical subspecialty training to complement the current academic subspecialty training in South Africa. A two-tiered training model was developed over time. The hurdles that had to be overcome were the development of a curriculum and academic capacity, acquisition of appropriate funding, acceptance and accreditation of the decentralised training facility, and lastly, registration of the fellowship with the Health Professions Council of South Africa. The end result of the trial programme was a two-year full-time training with supportive funding, or a four-year programme, where the subspecialists would spend three weeks of the month in their home practice environment, attached to an accredited unit, and the last week in an academic institution. Due to the trial program's success for the South African context and the potential of such model for the developing world, it was evident that the trial programme had to be tested to determine whether and how it can be implemented on a wider basis.

Introduction Rectovaginal endometriosis is a form of deep infiltrating endometriosis and accounts for 5%-10% of cases. It is a very difficult to treat and can be associated with severe complications. Objectives The aim was to document the outcomes of patients undergoing laparoscopic surgery for rectovaginal endometriosis. Methods A retrospective audit of 112 consecutive women undergoing laparoscopic surgery for rectovaginal endometriosis at Vincent Pallotti's Aevitas Fertility Clinic was undertaken. Women were identified from a surgical database using medical aid coding and a review of case notes. Patients were telephonically contacted to gather missing information and to assess further outcomes. Results The majority of surgeries were performed using the shaving technique, in keeping with international trends, whilst fourteen cases required a segmental resection owing to extensive disease. Complications included rectovaginal fistulas (3 cases), bowel injuries (2 cases), ureteric injury (1 case), a pelvic abscess (1 case), a blood transfusion (1 case) and the need for three urgent re-operations. Of the 71 patients desiring fertility, 39 (54.9%) fell pregnant. Twenty-seven (69.2%) were spontaneous conceptions. Conclusions Our outcomes are in keeping with complication rates quoted in the international literature. In trained hands, laparoscopic surgery at our unit is a valid option in the management of rectovaginal endometriosis with similar complication rates and outcomes to international standards.

Spinal cord injury (SCI) is a unique medical condition and occurs most commonly to young men who are at the peak of their reproductive health. Only 5% of SCI patients can father a child without medical intervention. Fertility problems are mainly due to erectile or ejaculatory disturbances and poor semen quality. Semen specimens characterized by normal sperm concentration but extremely impaired motility and viability. The pathophysiology is still poorly understood, and findings vary among studies regarding the underlying cause of sperm dysfunction.

Globozoospermia is a severe form of teratozoospermia associated with the absence of the acrosome. In about 1% of round-headed spermatozoa an acrosome may persist as a rudimentary structure. It is the absence of the acrosome that renders rounded headed spermatozoa incapable of initiating oocyte activation with consequent failure to achieve fertilisation due to deficiency of phospholipase C-zeta (PLC ), the oocyte activating factor. Persistence of the acrosomal bud in globozoospermia is associated with spontaneous oocyte activation using intra-cytoplasmic sperm injection (ICSI). Assisted oocyte activation using calcium ionophore-A23187 has been the main method by which couples with globozoospermia have hope for achieving a pregnancy. The technique has a reported 60% chance of successful oocyte activation. We describe a couple with total globozoospermia who achieved fertilisation using sequential combination of motile sperm organelle morphological examination (MSOME) and intra-cytoplasmic morphologically selected sperm injection (IMSI). Fertilisation was achieved followed by transfer of four embryos as dictated by the patient's age, but all embryos failed to implant. Concerns over the possible transmission of defective genes to the offspring of couples with globozoospermia treated with ICSI/IMSI or assisted oocyte activation remains unabated. Our case demonstrates the efficacy of MSOME/IMSI as a good alternative to calcium ionophore for assisted oocyte activation in globozoospermic couples.

Objective. To report the importance of public-private interaction (PPI) as a strategy to make assisted reproductive technology (ART) affordable.Methods. Design: Commentary. Setting: Reproductive Medicine Unit, Tygerberg Academic Hospital.Discussion. PPI together with simplified methods of IVF such as scaling down on personnel, mild ovarian stimulation protocols, oocyte retrieval without anaesthesia and simple embryo culture systems are strategies to make ART affordable and accessible.Conclusion. This article illustrates that PPI can be one of the strategies to make ART treatment a reality in settings with very limited resources.

Several biological mechanisms have been proposed to link endometriosis with infertility. All of the current proposed mechanisms are clearly pathological in their own way, but none have been shown to directly decrease fecundity in women. The causal relationship between the presence of endometriosis and sub fertility is supported by several arguments as suggested by D'Hooghe et al.

Osseous metaplasia should be kept in mind as a rare cause of failure to conceive, even in patients with primary infertility. We report a case of osseous metaplasia of the endometrium as a cause of primary infertility and present a literature review. The condition may be more common than expected or generally accepted, and should be kept in mind even in patients with primary infertility. Hysteroscopy is an effective diagnostic as well as treatment modality. The human endometrium contains populations of epithelial progenitor cells and mesenchymal stem cells. These cells are multipotent but rare, and are the most likely origin of the endometrial ossification. The cells can also differentiate into adipogenic and chondrogenic lineages.

Many variables may influence success rates after intrauterine insemination (IUI), including sperm quality in the native and washed semen sample. A literature search was performed to investigate the threshold levels of sperm parameters above which IUI pregnancy outcome is significantly improved and/or the cut-off values reaching substantial discriminative performance in an IUI programme. A search of MEDLINE, EMBASE and Cochrane Library revealed a total of 983 papers. Only 55 studies (5.6%) fulfilled the inclusion criteria and these papers were analysed. Sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value ⩾5% normal morphology; (iii) total motile sperm count in the native sperm sample: cut-off value of 5–10 million; and (iv) total motility in the native sperm sample: threshold value of 30%. The results indicate a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. More prospective cohort trials and prospective randomized trials investigating the predictive value of semen parameters on IUI outcome are urgently needed.It is generally believed that intrauterine insemination (IUI) with homologous semen should be a first-choice treatment to more invasive and expensive techniques of assisted reproduction in cases of cervical, unexplained and moderate male factor subfertility. The rationale for the use of artificial insemination is to increase gamete density at the site of fertilization. Scientific validation of this strategy is difficult because literature is rather confusing and inconclusive. Many variables may influence success rates after IUI treatment procedures. It seems logical that sperm quality has to be one of the main determinants to predict IUI success. Clinical practice would benefit from the establishment of threshold levels for sperm parameters above which IUI pregnancy outcome is significantly improved and below which a successful outcome is unlikely. We performed a literature search to investigate if such threshold levels are known. Most striking were the lack of standardization in semen-testing methodology and the huge heterogeneity of patient groups and IUI treatment strategies. The four sperm parameters most frequently examined were: (i) inseminating motile count after washing: cut-off value between 0.8 and 5 million; (ii) sperm morphology using strict criteria: cut-off value >4% normal morphology; (iii) total motile sperm count in native sperm sample: cut-off value of 5–10 million; and (iv) total motility in native sperm sample: threshold value of 30%. This review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI pregnancy rate.

Objective: To determine whether the presence of soluble human leukocyte antigen G (sHLA-G) affects implantation and pregnancy outcomes in vitro.Design: A multicenter retrospective study.Setting: Six certified in vitro fertilization (IVF) units.Patient(s): Embryos obtained from 2,040 patients from six different IVF clinics.Intervention(s): Soluble HLA-G determination on day-2 embryos after intracytoplasmic sperm injection, with embryos transferred on day 3 using the sHLA-G data.Main Outcome Measure(s): Ongoing pregnancy rate (10-to 12-week ultrasound finding).Result(s): All embryos were individually cultured, and a chemiluminescence enzyme-linked immunosorbent assay was used to detect the presence of sHLA-G in the culture medium surrounding the embryos. Embryos were selected based on a positive sHLA-G result and a graduated embryo scoring (GES) score >70, or on embryo morphology if the test was negative. In all centers, a positive sHLA-G result was associated with an increase in the odds of an ongoing pregnancy. The incidence of an ongoing pregnancy was 2.52 times greater in embryos transferred on day 3 with a positive sHLA-G test result than the incidence of an ongoing pregnancy in embryos with a negative sHLA-G test result.Conclusion(s): Data from this multicenter study confirm that sHLA-G expression is a valuable noninvasive embryo marker to assist in improving pregnancy outcomes, with the theoretical potential to reduce multiple pregnancies. (C) 2013 by American Society for Reproductive Medicine.

M.A. Belfort, Provo, Utah J. Bornstein, Nahariya H.L. Brown, Durham, N.C. C. Chapron, Paris J. de Haan, Maastricht G.A. Dekker, Adelaide, S.A. J.A. Deprest, Leuven K. Hecher, Hamburg S. Kahhale, São Paulo H. Kliman, New Haven, Conn. T.F. Kruger, Tygerberg J.A. Kuller, Raleigh, N.C. M.J. Kupferminc, Tel Aviv H. Minkoff , Brooklyn, N.Y. J. Moodley, Congella J.M. Mwenda, Nairobi H. Odendaal, Tygerberg J.T. Repke, Hershey, Pa. G.R. Saade, Galveston, Tex. B.M. Sibai, Cincinnati, Ohio S.K. Smith, London I.E. Timor-Tritsch, New York, N.Y. S. Uzan, Paris Johan Verhaeghe, Leuven J.J. Walker, Leeds G.D. Wendel, Dallas, Tex. R.A. Wild, Oklahoma City, Okla. G. Zador, Södertälje M.B. Zimmerman, Iowa City, Iowa Gynecological Ultrasound and Imaging George Condous, St. Leonards, N.S.W.

The aim of this study was to investigate the relationship between seminal leukocytes, reactive oxygen species (ROS) production in the ejaculate, and markers of apoptosis in human spermatozoa. Semen samples were collected from 60 patients attending fertility clinics at the Reproductive Biology Unit at Tygerberg Academic Hospital and Vincent Pallotti Hospital, Cape Town, South Africa. The concentration of seminal leukocytes was determined and was correlated with ROS production in the ejaculate, the percentage of superoxide (·O2(-))- and hydrogen peroxide (H2O2)-positive spermatozoa, glutathione activation in the ejaculate, and with markers of apoptosis in spermatozoa, namely cysteine-dependent aspartate-directed proteases (caspase)-3/7 activation, mitochondrial membrane potential (ΔΨm), and the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive sperm. Significant correlations with the concentration of seminal leukocytes were found for ROS production in the ejaculate, the percentage of ·O2(-)-positive spermatozoa, and caspase-3/7 activation in the ejaculate. Leukocytospermic samples showed significantly higher ROS production, percentage of ·O2(-)-positive sperm, GSH activation, and caspase-3/7 activation compared to non-leukocytospermic samples. The percentage of ·O2(-)-positive sperm was significantly correlated with sperm ΔΨm and caspase-3/7 activation in the ejaculate. Sperm ΔΨm and TUNEL-positive sperm did not correlate with seminal leukocyte concentration. Data demonstrate that high seminal leukocyte concentrations that leads to increased seminal ROS production, and is also associated with caspase activation in the male germ cell and increased mitochondrial ROS production. The latter could possibly be a result of disturbed ΔΨm. The activation of caspase-3/7 could then follow the increased intrinsic superoxide levels due to depleted intrinsic glutathione (GSH). These cellular events might not directly and immediately lead to DNA fragmentation as an endpoint of apoptosis because of topological hindrances.

We agree with the statements in the letter. We use this opportunity to highlight a few problem areas regarding the sHLA-G assay. It has been postulated by Hviid et al. (1Hviid T.V. Hylenius S. Lindhard A. Christiansen O.B. Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome.Tissue Antigens. 2004; 64: 66-69Crossref PubMed Scopus (120) Google Scholar) that sHLA-G plays a pivotal role during the implantation process. The presence of sHLA-G in spent media of individually cultured embryos and its influence on assisted reproductive technology outcomes have been reported by Sher et al. (2Sher G. Keskintepe L. Nouriani M. Roussev R. Batzofin J. Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of “embryo competency' and IVF outcome.Reprod Biomed Online. 2004; 9: 74-78Abstract Full Text PDF PubMed Scopus (113) Google Scholar) and in a meta-analysis by Vercammen et al. in 2008 (3Vercammen M.J. Verloes A. van de Velde H. Haentjens P. Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis.Hum Reprod Update. 2008; 14: 209-218Crossref PubMed Scopus (46) Google Scholar). The results of a prospective randomized trial (4Kotze D.J. Hansen P. Keskintepe L. Snowden E. Sher G. Kruger T. Embryo selection criteria based on morphology versus the expression of a biochemical marker (sHLA-G) and a graduated embryo score: prediction of pregnancy outcome.J Assist Reprod Genet. 2010; 27: 309-316Crossref PubMed Scopus (14) Google Scholar) followed by a multicenter (5Kotze D. Kruger T.F. Lombrd C. Padayachee T. Keskintepe L. Sher G. The effect of the biochemical marker soluble human leukocyte antigen G on pregnancy outcome in assisted reproductive technology—a multicenter study.Fertil Steril. 2013; 100: 1303-1309Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar) approach confirmed our previous findings.Lately, the quest to find the best way to identify an embryo with the highest potential to develop into a live baby has been an issue of active debate. Notwithstanding the patient population that undoubtedly needs preimplantation genetic screening/preimplantation genetic diagnosis, there is a desperate need to establish criteria for a noninvasive method to be implemented to achieve the goal of identifying such embryos for transfer. We have shown that embryos transferred on day 3 (with good morphology) that have a positive expression of sHLA-G had superior outcome compared with embryos that were transferred based on morphology only. That said, we further suggest that transferring blastocysts with a positive sHLA-G expression might be even more superior.We highlighted shortfalls in the current publication. To apply this assay effectively, all embryos have to be cultured and tracked individually to specifically identify the “correct” embryo(s) for transfer. A positive aspect of applying this assay is the potential to transfer fewer embryos (even a single blastocyst) without compromising pregnancy outcome and simultaneously to reduce the risk of multiple pregnancies.Owing to the lack of standardization, it is our belief that a standardized sHLA-G assay with a specifically defined range (for positive sHLA-G expression) and standard “measuring units” should be established through international collaboration. This relatively inexpensive noninvasive approach could shift the paradigm for identifying the most competent embryos for transfer and to achieve the above-mentioned goal. We agree with the statements in the letter. We use this opportunity to highlight a few problem areas regarding the sHLA-G assay. It has been postulated by Hviid et al. (1Hviid T.V. Hylenius S. Lindhard A. Christiansen O.B. Association between human leukocyte antigen-G genotype and success of in vitro fertilization and pregnancy outcome.Tissue Antigens. 2004; 64: 66-69Crossref PubMed Scopus (120) Google Scholar) that sHLA-G plays a pivotal role during the implantation process. The presence of sHLA-G in spent media of individually cultured embryos and its influence on assisted reproductive technology outcomes have been reported by Sher et al. (2Sher G. Keskintepe L. Nouriani M. Roussev R. Batzofin J. Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of “embryo competency' and IVF outcome.Reprod Biomed Online. 2004; 9: 74-78Abstract Full Text PDF PubMed Scopus (113) Google Scholar) and in a meta-analysis by Vercammen et al. in 2008 (3Vercammen M.J. Verloes A. van de Velde H. Haentjens P. Accuracy of soluble human leukocyte antigen-G for predicting pregnancy among women undergoing infertility treatment: meta-analysis.Hum Reprod Update. 2008; 14: 209-218Crossref PubMed Scopus (46) Google Scholar). The results of a prospective randomized trial (4Kotze D.J. Hansen P. Keskintepe L. Snowden E. Sher G. Kruger T. Embryo selection criteria based on morphology versus the expression of a biochemical marker (sHLA-G) and a graduated embryo score: prediction of pregnancy outcome.J Assist Reprod Genet. 2010; 27: 309-316Crossref PubMed Scopus (14) Google Scholar) followed by a multicenter (5Kotze D. Kruger T.F. Lombrd C. Padayachee T. Keskintepe L. Sher G. The effect of the biochemical marker soluble human leukocyte antigen G on pregnancy outcome in assisted reproductive technology—a multicenter study.Fertil Steril. 2013; 100: 1303-1309Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar) approach confirmed our previous findings. Lately, the quest to find the best way to identify an embryo with the highest potential to develop into a live baby has been an issue of active debate. Notwithstanding the patient population that undoubtedly needs preimplantation genetic screening/preimplantation genetic diagnosis, there is a desperate need to establish criteria for a noninvasive method to be implemented to achieve the goal of identifying such embryos for transfer. We have shown that embryos transferred on day 3 (with good morphology) that have a positive expression of sHLA-G had superior outcome compared with embryos that were transferred based on morphology only. That said, we further suggest that transferring blastocysts with a positive sHLA-G expression might be even more superior. We highlighted shortfalls in the current publication. To apply this assay effectively, all embryos have to be cultured and tracked individually to specifically identify the “correct” embryo(s) for transfer. A positive aspect of applying this assay is the potential to transfer fewer embryos (even a single blastocyst) without compromising pregnancy outcome and simultaneously to reduce the risk of multiple pregnancies. Owing to the lack of standardization, it is our belief that a standardized sHLA-G assay with a specifically defined range (for positive sHLA-G expression) and standard “measuring units” should be established through international collaboration. This relatively inexpensive noninvasive approach could shift the paradigm for identifying the most competent embryos for transfer and to achieve the above-mentioned goal. Focus on the importance of soluble human leukocyte antigen G as a marker for embryo selection in assisted reproductive technologyFertility and SterilityVol. 100Issue 6PreviewWe have read with interest the paper by Kotze et al. (1), reporting the retrospective analysis of 2,040 patients for the expression of soluble human leukocyte antigen G (sHLA-G) by day 2 embryos after intracytoplasmic sperm injection. The data represent further confirmation of the role of sHLA-G molecule quantification in embryo culture supernates as a marker for embryo selection (2). In pregnancy, several tolerance mechanisms have been demonstrated to counteract the maternal immune response. Among these, the expression of HLA-G by invasive cytotrophoblasts has been shown to play a fundamental role in creating a tolerogenic condition at the fetal-maternal interface (2). Full-Text PDF