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Sperm Transport from the External Cervical Os to the Fallopian Tubes in Women: A Time and Quantitation Study
Abstract
PIP
Sperm transport was characterized on optimal, controlled, assessable conditions in this study. Subjects were women who had requested surgical sterilization. All subjects were restricted from coitus for 11-14 days preoperatively. The study was performed within 36 hours of the estradiol preovulatory peak for each subject; so surgical excision of both fallopian tubes was accomplished at predetermined times after insemination with fresh, whole, high-quality ejaculates; the cervical mucus column was also removed. Using this technique, sperms were identified in the oviduct within 5 minutes from deposition in the proximal vagina. Numbers of sperm in the oviduct were directly related to numbers inseminated. Sperm distribution was throughout the oviduct and was highest in fimbria (tubes had been divided in thirds upon excision). For 15-45 minutes after insemination, a constant level of sperm existed in the oviduct. 1 subject was studied similarly to determine the presence of sperm in endometrium, and no sperm occurred in that cavity until 80 minutes after insemination. This study also reports the total numbers of sperm present in cervical mucus and the correlation of insemination and time after insemination.
... The time elapsed to achieve complete agglutination (i.e., 100% agglutinated sperm), was recorded. Since it has been reported that sperm can reach the endocervical canal in 3-5 minutes, a cutoff time of 2.5 min was used for the assay [4,29,30]. Data points were acquired in triplicate and the experiment was repeated three times using semen from different donors. ...
... Differences in Fc-mediated functions between HCA and HCA-LALAPG were observed. Some antisperm antibodies can immobilize sperm in the presence of a complement source [30,31]. We have previously shown the ability of HCA to immobilize sperm in a concentration dependent manner in the presence of human serum (complement source) [4]. ...
High rates of unintended pregnancies worldwide indicate a need for more accessible and acceptable methods of contraception. We have developed a monoclonal antibody, the Human Contraception Antibody (HCA), for use by women in vaginal films and rings for contraception. The divalent F(ab')2 region of HCA binds to an abundant male reproductive tract-specific antigen, CD52g, and potently agglutinates sperm. Certain other antibody activities mediated by the Fc region such as mucus trapping, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) could have beneficial or negative effects. The purpose of this study was to document HCA Fc effector functions and determine whether an engineered variant of HCA with a modified Fc region, HCA-LALAPG, retains desirable contraceptive activity while minimizing Fc-mediated effects. Fab and Fc functions were compared between HCA and HCA-LALAPG. Fab activity was assessed using sperm agglutination and modified swim-up ("sperm escape") assays. Fc functions were assessed by CDC (sperm immobilization), ADCP, and cervical mucus penetration assays. HCA and HCA-LALAPG showed equivalent activity in assays of Fab function. In the assays of Fc function, HCA supported strong CDC, ADCP, and sperm trapping in cervical mucus whereas HCA-LALAPG demonstrated little to no activity. HCA and the HCA-LALAPG variant were both highly effective in the sperm agglutination assays but differed in Fc mediated functions. Use of the HCA-LALAPG variant for contraception in women could reduce antibody-mediated inflammation and antigen presentation but may have reduced contraceptive efficacy due to much weaker sperm trapping in mucus and complement-dependent sperm immobilization activity.
... After 2 min, a small Pederson vaginal speculum was used to expose the vaginal pool of secretions for collection and for examination of the vagina with a colposcope (Leisegang Model 3MTL-LED) for assessment of the vaginal mucosa. An early 2-min timepoint was selected for testing products that act within the vagina due to the rapid transport of sperm to the Fallopian tubes within 5 min of insemination [14]. ...
... sperm to the Fallopian tubes [14]. Capacitation, a process that can take several hours, appears to occur within the cervical mucus and upper tract, after sperm transit from the vagina to the cervix [18]. ...
Background:
High unintended pregnancy rates are partially due to lack of effective nonhormonal contraceptives; development of safe, effective topical vaginal methods will address this need. Preclinical product safety and efficacy assessment requires in vivo testing in appropriate models. The sheep is a good model for the evaluation of vaginally delivered products due to its close similarities to humans. The study objective was to develop an ovine model for efficacy testing of female nonhormonal contraceptives that target human sperm.
Methods:
Fresh human semen was pooled from male volunteers. Nonpregnant female Merino sheep were treated with control or vaginal contraceptive product (IgG antibody with action against sperm or Nonoxynol-9 [N9]). Pooled semen was added to the sheep vagina and mixed with product and vaginal secretions. Microscopic assessment of samples was performed immediately and progressive motility (PM) of sperm was compared between treatments. Cytokines CXCL8 and IL1B were assessed in vaginal fluid after instillation of human semen.
Results:
No adverse reactions or elevations in proinflammatory cytokines occurred in response to human semen. N9 produced signs of acute cellular toxicity while there were no cellular changes after IgG treatment. N9 and IgG had dose-related effects with the highest dose achieving complete sperm immobilization (no sperm with PM).
Discussion:
Surrogate post-coital testing of vaginally administered contraceptives that target human semen was developed in an ovine model established for vaginal product preclinical testing. This expanded model can aid the development of much needed nonhormonal topical vaginal contraceptives, providing opportunities for rapid iterative drug development prior to costly, time-intensive human testing.
... The rationale of IUI Decades ago very disappointing results were reported regarding the capacity of motile spermatozoa to reach the oviduct after intercourse with an important reduction in sperm number along the length of the female reproductive tract (Settlage et al., 1973;Mortimer and Templeton, 1982). According to Settlage et al. (1973) only 0.1% of spermatozoa placed in the upper vagina were also present in the cervical canal, 1 h after insemination. ...
... The rationale of IUI Decades ago very disappointing results were reported regarding the capacity of motile spermatozoa to reach the oviduct after intercourse with an important reduction in sperm number along the length of the female reproductive tract (Settlage et al., 1973;Mortimer and Templeton, 1982). According to Settlage et al. (1973) only 0.1% of spermatozoa placed in the upper vagina were also present in the cervical canal, 1 h after insemination. Even more striking was the finding that only 1 in every 14 million motile sperm deposited in the vagina reached the site of fertilization in the oviduct. ...
Background:
IUI with or without ovarian stimulation (OS) has become a first-line treatment option for many infertile couples, worldwide. The appropriate treatment modality for couples and their clinical management through IUI or IUI/OS cycles must consider maternal and perinatal outcomes, most notably the clinical complication of higher-order multiple pregnancies associated with IUI-OS. With a current global emphasis to continue to decrease maternal and perinatal mortality and morbidity, the World Health Organization (WHO) had established a multi-year project to review the evidence for the establishment of normative guidance for the implementation of IUI as a treatment to address fertility problems, and to consider its cost-effectiveness for lower resource settings.
Objective and rationale:
The objective of this review is to provide a review of the evidence of 13 prioritized questions that cover IUI with and without OS. We provide summary recommendations for the development of global, evidence-based guidelines based upon methodology established by the WHO.
Search methods:
We performed a comprehensive search using question-specific relevant search terms in May 2015. For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO, specific search terms were used to find the available evidence in MEDLINE (1950 to May 2015) and The Cochrane Library (until May 2015). After presentation to an expert panel, a further hand search of references in relevant reviews was performed up to January 2017. Articles that were found to be relevant were read and analysed by two investigators and critically appraised using the Cochrane Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic reviews. The quality of the evidence was assessed using the GRADE system. An independent expert review process of our analysis was conducted in November 2016.
Outcomes:
This review provides an assessment and synthesis of the evidence that covers 13 clinical questions including the indications for the use of IUI versus expectant management, the sperm parameters required, the best and optimal method of timing and number of inseminations per cycle, prevention strategies to decrease multiple gestational pregnancies, and the cost-effectiveness of IUI versus IVF. We provide an evidence-based formulation of 20 recommendations, as well as two best practice points that address the integration of methods for the prevention of infection in the IUI laboratory. The quality of the evidence ranges from very low to high, with evidence that may be decades old but of high quality, however, we further discuss where critical research gaps in the evidence remain.
Wider implications:
This review presents an evidence synthesis assessment and includes recommendations that will assist health care providers worldwide with their decision-making when considering IUI treatments, with or without OS, for their patients presenting with fertility problems.
... Above all, a most puzzling question is the underlying fertility enhancing mechanism of immobilization following IUI, which remains unclear. Spermatozoa can reach the Fallopian tube within 5 min after intravaginal insemination (Settlage et al., 1973). Furthermore, they can survive for days in the cervical crypts (Suarez and Pacey, 2006). ...
... What we know from earlier studies is that sperm cells can reach the Fallopian tube within 5 min after intravaginal insemination. Sperm migration through the cervical canal is accomplished by the spermatozoon itself, but above the internal os sperm ascent is the result of both active swimming and passive transport by uterine contractions (Settlage et al., 1973). It is unclear whether gravity affects this movement, let alone immobilization of 15 min. ...
Study question:
Does 15 min of immobilization after IUI improve pregnancy rates?
Summary answer:
Immobilization for 15 min after IUI does not improve pregnancy rates.
What is known already:
Prior RCTs report a beneficial effect of supine immobilization for 15 min following IUI compared to immediate mobilization, however, these studies can be criticized. Given the importance for the logistics in daily practice and the lack of biological plausibility we planned a replication study prior to potential implementation of this procedure.
Study design, size, duration:
A single centre RCT, based in an academic setting in the Netherlands, was performed. Participants were randomly assigned for 15 min of supine immobilization following IUI for a maximum of six cycles compared to the standard procedure of immediate mobilization following IUI. Participants and caregivers were not blinded to group assignment. An independent researcher used computer-generated tables to allocate treatments. Stratification occurred to the indication of IUI (unexplained or mild male subfertility). Revelation of allocation took place just before the insemination by the caregiver. The primary outcome was ongoing pregnancy rate per couple.
Participants/materials, setting, methods:
A total of 498 couples diagnosed with unexplained or mild male subfertility and an indication for treatment with IUI were approached and randomized in the study, of which 244 participants were assigned to 15 min of supine immobilization and 254 participants to immediate mobilization.
Main results and the role of chance:
Participant characteristics were comparable between the groups, and 236 participants were analysed in the immobilization group, versus 245 in the mobilization group. The ongoing pregnancy rate per couple was not found to be superior in the immobilization group (one-sided P-value = 0.97) with 76/236 ongoing pregnancies (32.2%) being accomplished in the immobilization and 98/245 ongoing pregnancies (40.0%) in the immediate mobilization group (relative risk 0.81; 95% CI [0.63, 1.02], risk difference: -7.8%, 95% CI [-16.4%, 0.8%]). No difference was found in miscarriage rate, multiple gestation rate, live birth rate and time to pregnancy between the groups.
Limitations, reasons for caution:
Owing to discontinuation of the planned treatment not all participants reached six IUI cycles or an ongoing pregnancy. However, this is as expected in IUI treatment and mirrors clinical practice. These participants were equally distributed across the two groups. Women with tubal pathology and endocrine disorders were excluded for this trial, and this might narrow generalizability.
Wider implications of the findings:
This study shows no positive effect of 15 min of immobilization following IUI on pregnancy rates. Based on available evidence today, including our study, a possible beneficial effect of supine immobilization after IUI is at least doubtful and straightforward implementation does not seem to be justified.
Study funding/competing interest(s):
No funding was received. All authors have nothing to disclose.
Trial registration number:
Dutch Trial Register NTR 2418.
Trial registration date:
20 July 2010.
Date of first patient’s enrolment:
11 August 2010.
... Evidence of transient exposure to microbial commensals or pathogens has been reported in the upper genital tract [142][143][144][145]. Microorganisms have been isolated from the endometrial cavity in both the presence and the absence of symptoms of infection and/or inflammation, suggesting that the presence of microorganisms within the upper genital tract may not always reflect a pathological process; rather the endometrial cavity is not sterile, and harbours an endogenous microbiota [146][147][148][149][150]. Cultures of vaginal and endocervical specimens have proven to be poor indicators of the presence of microorganisms within the endometrial cavity and discordant results for microbial species were obtained when sampling both sites in asymptomatic women [151,152]. ...
... This indicates a hormonal control over uterine peristalsis and thus rapid sperm transport [12]. Studies are limited because of possible artifacts by invasive techniques, such as anesthesia and laparotomy [13,14]. These methodological disadvantages can be eliminated with the use of HSSG because this method allows the study of utero-tubal transport in vivo, without stress and injury. ...
Objective
To evaluate the diagnostic accuracy of a bygone method, hystero-salpingo-scintigraphy (HSSG), for tubal patency assessment of infertile women.
Material and methods
Prospective cohort study involving women in the infertility workup at the University of Debrecen, Hungary. Seventy infertile patients were scheduled to either basic dynamic HSSG, post-purge dynamic HSSG, or post-purge dynamic HSSG followed by SPECT/CT for reducing tracer contamination. The primary endpoint was the evaluation of the diagnostic accuracy of HSSG for the three methods.
Results
During the basic dynamic group, the examination yielded a sensitivity of 87.5%, with a specificity of 71.7%, while positive and negative predictive values were 31.8%, and 97.4% respectively. Using post purge dynamic HSSG, it resulted in a sensitivity of 87.5%, a specificity of 88.7%, a positive predictive value of 53.8%, and a negative predictive value of 97.9%. Adding SPECT/CT to post-purge dynamic HSSG increased diagnostic accuracy with 100% sensitivity and 88.7% specificity, while positive and negative predictive values were 57.1% and 100%, respectively.
Conclusion
HSSG is a non-invasive and well-tolerated technique for tubal patency. It could be used initially to predict tubal patency in case of infertility. Its diagnostic accuracy is higher when it is carried out by adding SPECT/CT to the post-purge dynamic method.
... For effective vaginal immunocontraception, mAbs must agglutinate/immobilize sperm before they reach the upper reproductive tract; thus, the speed with which PM sperm become agglutinated will likely correlate with contraceptive efficacy (33). We, therefore, quantified the kinetics of sperm agglutination immediately following mixing of sperm and mAb using CASA with washed sperm at a standard concentration of 5 million PM sperm/mL. ...
Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.
... The swimming speed of sperm in aqueous medium is about 5 mm/min [32]. Although the time taken by the sperm to traverse the uterine cavity is variable and difficult to assess, sperm have been recovered from the Fallopian tube within 5-10 minutes of insemination [33][34][35]. Transport of sperm through the uterus might be enhanced by pro-ovarian myometrial contractions that might be stimulated by seminal components [36][37][38]. Myometrial contractions may draw sperm and watery midcycle mucus from the cervix into the uterus [39]. ...
... O f the 200-600 million sperm deposited near the cervical canal during sexual intercourse only a few hundred will complete the journey to the uterine tubes taking 5-45 minutes, with the majority of the remainder becoming non-viable after 24 hours (Settlage et al., 1973). Prior to this human sperm undergo capacitation in the female genital tract, a prerequisite for fertilisation whereby glycoproteins are lost from the acrosomal region and motility increases (de Lamirande et al., 1997). ...
Preimplantation genetic diagnosis (PGD) involves the genetic screening of cleavage-stage embryos generated by in vitro fertilisation (IVF), and has been introduced for couples at high risk of transmitting a genetic defect many of whom have experienced recurrent spontaneous or induced abortion. Prompted by growing patient demand, this study has centred on developing new approaches for PGD of chromosomal abnormalities using fluorescent in situ hybridisation (FISH). Dual and triple combinations of locus-specific FISH probes for chromosomes 13, 14, 15, 18 and 21 were developed, and evaluated in seventy-one surplus IVF embryos. In the normally developing group (43 embryos), 67% were uniformly normal, 19% were diploid mosaic, 9% were aneuploid mosaic and 5% were chaotic. In the abnormally developing group (28 embryos), 21% were normal and 79% were chromosomally abnormal. PGD strategies were designed for fifty referrals involving chromosomal indications, 12% of which reached the embryo biopsy stage of PGD whilst 18% are awaiting treatment. Over two thirds withdrew from further treatment, reasons included: 26% losing contact with the Centre, 16% naturally conceived normal pregnancy, 10% electing for alternative treatment, 10% personal circumstances and 8% IVF-related problems. Six couples underwent PGD, one gonadal mosaic for trisomy 21, two balanced reciprocal translocation carriers and three Robertsonian translocation carriers. Over ten IVF cycles, a total of 160 oocytes were retrieved and 72% (53/74) of resulting embryos were biopsied. FISH analysis showed 15% of embryos were normal for the chromosomes tested, whilst 85% were chromosomally unbalanced, categorised as 50% aneuploid/mosaic and 35% chaotic. No clinical pregnancies resulted from three single and three double embryo transfers. From these data three distinct mechanisms were identified which appear to be implicated in the reproductive problems experienced by these patients: gonadal mosaicism with precocious chromatid segregation; increased abnormal meiotic segregation associated with terminal translocation breakpoints; and a high incidence of chaotic chromosome distribution and division in early cleavage-stages.
... EVALUACION DEL FACTOR MASCULINO 1. Espermograma: En un eyaculado normal, 80 a 500 millones de espermatozoides son depositados en el tracto reproductor femenino . Cada espermatozoide normal tiene la capacidad de penetrar el cuello uterino, ascender por la cavidad endometrial, alcanzar las trompas de Falopio y progresar por las mismas hasta alcanzar el sitio de la fertilización en la porción distal de las mismas, en un tiempo mínimo de 15 minutos (14). ...
La incidencia de la Infertilidad Involuntaria en América ha sido calculada entre el 1O y 15% de todos los matrimonios (1, 2, 3). Infertilidad es la inhabilidad para procrear, mientras que esteriliciad describe el estado de una persona cuya capacidad para reproducirse ha sido considerada irreversible (ejemplo, disgenesia gonadal, ausencia congénita de útero, etc.). Infertilidad primaria significa que la paciente nunca ha quedado embarazada e Infertilidad secundaria implica que al menos ha habido una concepción (1, 2, 3, 4). La inhabilidad para procrear puede ser el resultado de fallas para concebir o de fallas para que el producto crezca y se desarrolle hasta la viabilidad. Aunque el último problema es importante representa muy poca proporción de casos de infertilidad por lo cual aquí enfatizaremos los aspectos relacionados con las fallas en la concepción.
... For effective contraception, sperm must be stopped in mucus before they can swim through the cervix and access the uterus. [22] This suggests Abs that could agglutinate sperm more quickly should provide more effective contraception. Thus, we next quantified the sperm agglutination kinetics of both constructs using CASA by measuring the fraction of agglutinated and free PM sperm over time immediately after mixing washed sperm with different mAbs. ...
Millions of women avoid using available contraceptives and risk unintended pregnancies every year, due to perceived and/or real side-effects associated with the use of exogenous hormones. Naturally occurring anti-sperm antibodies can prevent fertilization in immune infertile women by limiting sperm permeation through mucus, particularly multivalent antibodies such as sIgA that offers robust agglutination potencies. Unfortunately, sIgA remains challenging to produce in large quantities and easily aggregates. Here, we designed two tetravalent anti-sperm IgGs with a Fab domain previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscore the multimerization of IgG as a promising strategy to improve existing mAb therapeutics.
... For effective vaginal immunocontraception, mAbs must agglutinate/immobilize sperm before they reach the upper reproductive tract; thus, the speed with which PM sperm become agglutinated will likely correlate with contraceptive efficacy 31 . We therefore quantified the kinetics of sperm agglutination immediately following mixing of sperm and mAb using CASA with washed sperm at a standard concentration of 5 million PM sperm/mL. ...
Many women risk unintended pregnancy due to dissatisfaction with available hormonal contraceptive methods. This led us to pursue topical sperm-binding monoclonal antibodies as a strategy for safe, non-hormonal contraception. Motivated by the greater agglutination potencies of polymeric immunoglobulins such as IgM and the exceptional bioprocessing ease in manufacturing IgG, we engineered IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster than the parent IgG at agglutinating sperm, while preserving Fc-mediated trapping of individual spermatozoa in mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using 33 micrograms of the 10 Fab HM-IgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.
... Spermatozoa are small and mobile cells and inseminated fluid contains millions of spermatozoa. It has been shown that sperms reach fallopian tubes only a few minutes after intercourse or intrauterine insemination [26]. That is, spermatozoa can survive exhausting uterine contractions and expulsion by virtue of this progressively motile property. ...
Objective:
Intrauterine insemination (IUI) is frequently used to treat patients with ovulation disorders, cervical factor, mild male infertility and unexplained infertility. The aim of this study was to investigate the impact of modified speculum application on the success of IUI in patients with unexplained infertility.
Materials and methods:
This prospective randomized study reviewed 219 women who had undergone controlled ovarian hyperstimulation (COH)-IUI treatment. In the modified speculum application group (109 patients with 124 cycles), the screw of the vaginal speculum was loosened after passing the internal os with catheter and the vaginal speculum remained in this position to ensure closure of the cervix during the procedure. In the conventional speculum application group (110 patients with 132 cycles), the screw of the vaginal speculum was not loosened to close the lips of cervix after passing the internal os with the catheter and the vaginal speculum was removed after withdrawal of the insemination catheter. The primary outcome was live birth rate.
Results:
The modified and conventional speculum application groups had statistically similar demographic and clinical characteristics. There were no significant differences between the study and the control groups in terms of the clinical pregnancy rate per cycle and per patient (24.1% vs 18.9% and 26.6% vs 22.7%, respectively), as well as the live birth rate per cycle and per patient (19.3% vs 15.1% and 22% vs 18.1% respectively).
Conclusion:
Applying gentle mechanical pressure on the portio vaginalis of the cervix using a vaginal speculum during IUI does not improve pregnancy and live birth rates in patients with unexplained infertility.
... The 10% (v/v) lubricant dilution is reflective of the concentration used in previously published studies [2,12,14]. The range of incubation times chosen are consistent with a previously published study suggesting that the majority of fertilising sperm migrate through the cervix within 30 minutes after ejaculation [23]. In subsequent experiments, motile sperm fractions from n = 5 different donors were incubated for 10 minutes at 37˚C in 10% (v/ v), 5% (v/v), 1% (v/v) and 0.2% (v/v) solution of Aquagel. 10 minutes was chosen as this was the earliest point at which we had previously observed changes in progressive motility following incubation with 10% (v/v) Aquagel. ...
Vaginal lubricants are commonly used by couples trying-to-conceive. However, most vaginal lubricants are sperm toxic and therefore should not be used by couples trying-to-conceive. Despite this, lubricant sperm toxicity is insufficiently reported and guidance for healthcare professionals (HCPs) is absent. In this study, lubricant-related practices of fertility based HCPs in Scotland were sampled via an online survey. Lubricants identified as being utilised in the fertility setting were subsequently incubated with prepared sperm samples to establish effects on sperm motility. HCP recommendations (n = 32) on lubricant use were varied although knowledge related to sperm toxicity was generally poor. HCPs infrequently asked about lubricant use and were unaware of guidance in this area. Aquagel, the only prescribed lubricant identified in this study, reduced sperm progressive motility to 49% of control after 10 minutes, even at concentrations as low as 5%. Vitality testing suggested the deterioration in progressive motility with Aquagel was not as a result of cell death. Conversely , Pré Vaginal Lubricant, a 'sperm-safe' lubricant, did not significantly affect any markers of sperm function assessed. Development of clinical guidance in this area is recommended to ensure HCPs deliver informed advice as lubricant use in couples trying-to-conceive may inadvertently contribute to delay in conception.
... 19 Another study has documented that within 15 minutes after the coitus, a constant level of sperm exists in the oviduct. 20 Still regarding intercourse, the presence or absence of female orgasm does not seem to alter the probability of conception. 12 ...
Considering that myths and misconceptions regarding natural procreation spread rapidly in the era of easy access to information and to social networks, adequate counseling about natural fertility and spontaneous conception should be encouraged in any kind of health assistance. Despite the fact that there is no strong-powered evidence about any of the aspects related to natural fertility, literature on how to increase the chances of a spontaneous pregnancy is available. In the present article, the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO, in the Portuguese acronym) Committee on Endocrine Gynecology provides suggestions to optimize counseling for non-infertile people attempting spontaneous conception.
Resumo
Uma vez que mitos e equívocos sobre a procriação natural se espalham rapidamente na era do fácil acesso à informação e às redes sociais, o aconselhamento adequado sobre a fertilidade natural e a concepção espontânea deve ser encorajado em qualquer tipo de assistência à saúde. Apesar do fato de não haver evidências fortes sobre qualquer dos aspectos relacionados à fertilidade natural, existe literatura sobre como aumentar as chances de uma gravidez espontânea. No presente artigo, a Comissão Nacional de Ginecologia Endócrina da Federação Brasileira das Associações de Ginecologia e Obstetrícia (FEBRASGO) oferece sugestões para otimizar o aconselhamento a pessoas que tentam a concepção espontânea, na ausência do diagnóstico de infertilidade.
... The number of sperm passing through each oviduct increases gradually to a peak 2 days after insemination (Settlage, Motoshima, & Tredway, 1973) and then steadily declines, the last fertile sperm evidently not leaving the ampullae until 5 days after insemination (Wilcox, Weinberg, & Baird, 1995). In total, therefore, there are potentially 6 days in the human menstrual cycle on which a single insemination can lead to fertilization (Wilcox et al., 1995). ...
... Intrauterine insemination (IUI) is an assisted conception technique offering hope to many infertile couples based on the finding of a striking reduction in sperm number with the length of the female reproductive tract after intercourse (1). It is performed by transferring a processed motile semen sample into a female's uterus, which increases the number of sperm that reaches the oviduct and subsequently increases the chances of in vivo fertilization. ...
To compare the clinical outcomes of intrauterine insemination (IUI) with or without ovulation induction (OI), IUI cycles from January 2008 to December 2017 in Zhoushan Maternity and Child Healthcare Hospital were included, consisting of 455 natural cycles and 536 OI cycles. The overall clinical pregnancy rate did not differ between the two groups (P > 0.05). Stratified by OI medications such as clomiphene (CC), human menopausal gonadotropin (HMG) and follicle stimulating hormone (FSH), the pregnancy rates in HMG, CC, CC+HMG, and FSH/FSH+HMG groups were 11.70%, 13.58%, 15.95%, and 13.46%, respectively, but the difference was not significant compared with natural cycles (P > 0.05). Stratified by infertility etiology, the pregnancy rate was significantly higher in stimulated cycles than natural cycles with ovulation disorders (P < 0.01) and unexplained factors (P < 0.01) while it was significantly lower regarding cervical factors (P < 0.01), endometriosis (P < 0.05), male factor (P < 0.01) and other female factors. There was no strong difference of pregnancy rate for biparental causes (P > 0.05). Stratified by age category, women over 35 had higher pregnancy rate in stimulated cycles compared with natural cycles (18.75 vs. 12.24%; P < 0.05), while women under 35 had no significant difference of pregnancy rate between the two groups (13.65 vs 13.05%; P > 0.05). However, there was no significant difference between each ovarian stimulation group and natural cycle group regardless of the infertility causes or age categories. To conclude, IUI-OI could achieve a higher overall pregnancy rate for women over 35 and infertile patients with ovulation disorders and unexplained factors.
... The WHO guideline provides no recommendations for bed rest after IUI (WHO, 2010). The rationale for a positive impact of a short period of supine positioning after insemination is that the spermatozoa may reach the fallopian tube within only 10 min (Settlage et al., 1973). Immediate mobilization might counteract this movement due to gravity (Ledger, 2009). ...
Study question:
Are the guidelines for the technical aspects of IUI (WHO, 2010) still in accordance with the current literature?
Summary answer:
In general, the laboratory guidelines of the World Health Organization (WHO) are a suitable protocol, although the evidence is not always conclusive and some changes are advisable.
What is known already:
Lack of standardization of the technical procedures required for IUI might result in inter-laboratory variation in pregnancy rates. Most centers still use their own materials and methods even though some guidelines are available.
Study design, size, duration:
A structural review focusing on the association between pregnancy rates and the procedures of semen collection (e.g. ejaculatory abstinence, collection place), semen processing (e.g. preparation method, temperature during centrifugation/storage), insemination (e.g. timing of IUI, bed rest after IUI) and the equipment used.
Participants/materials, setting, methods:
A literature search was performed in Medline and the Cochrane library. When no adequate studies of the impact of a parameter on pregnancy results were found, its association with sperm parameters was reviewed.
Main results and the role of chance:
For most variables, the literature review revealed a low level of evidence, a limited number of studies and/or an inadequate outcome measure. Moreover, the comparison of procedures (i.e. semen preparation technique, time interval between semen, collection, processing and IUI) revealed no consensus about their results. It was not possible to develop an evidence-based, optimal IUI treatment protocol.
Limitations, reasons for caution:
The included studies exhibited a lack of standardization in inclusion criteria and methods used.
Wider implications of the findings:
This review emphasizes the need for more knowledge about and standardization of assisted reproduction technologies. Our literature search indicates that some of the recommendations in the laboratory guidelines could be adapted to improve standardization, comfort, quality control and to cut costs.
Study funding/competing interest(s):
The Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands. S.K. and W.N. have no conflicts of interest to disclose. C.B. and A.W. are members of the board of the SKML. With a grant from SKML, L.L. was paid for her time to perform the research and write the publication. D.B. received grants from Merck Serono, Ferring and MSD, outside the submitted work.
Registration number:
N/A.
... Spermatoozoon enters the cervical mucus within the few minutes after the natural intercourse [9] and reaches the fallopian tubes within 10 minutes [10][11][12] preserving its fertilization capacity up to 8 days. As expected, its fertilization capacity decreases with time [1,13]. ...
Objective: Fertilization capacity of capacitated sperm decreases exponentially over time, but the reason is still under investigation. The aim of the study was to analyze the effect of prolonged incubation and temperature on sperm fertilization capacity with motility and staining parameters of phospholipase C-zeta (PLCZ), which is considered to be the oocyte activation factor. Materials and Methods: Density gradient washing was applied to semen of 11 infertile patients without severe oligoasthenospermia out of 16 patients. The samples were divided and cultured either at room temperature or at 37°C for 3 days. The spermatozoons were evaluated for motility, PLCZ staining and intensity daily. Results: All parameters decreased both at room and body temperature with increased incubation time. There was a strong correlation between the change in motility and in the percentage of PLCZ stained sperms, but this correlation decreased with incubation time. Conclusion: Prolonged incubation results show the correlation between PLCZ staining parameters and motility. Routine use of PLCZ staining together with semen analysis, will be useful to predict fertilization capacity of the sperm especially for unexplained infertility and fertilization failure cases, and also can increase the success of assisted reproductive technologies (ART) cycles.
... The number of sperm passing through each oviduct increases gradually to a peak 2 days after insemination (Settlage, Motoshima, & Tredway, 1973) and then steadily declines, the last fertile sperm evidently not leaving the ampullae until 5 days after insemination (Wilcox, Weinberg, & Baird, 1995). In total, therefore, there are potentially 6 days in the human menstrual cycle on which a single insemination can lead to fertilization (Wilcox et al., 1995). ...
Objectives:
The phrase "level of sperm competition" is used only vaguely in the primate literature. There is also little distinction between the important elements of frequency and intensity of sperm competition, largely because the two current forms of measurement (socio-sexual system and relative testes size) are both proxies which allow neither precision nor fine distinctions. Both measures have critics, socio-sexual system in particular being branded subjective, misleading, and changeable. Testes size is considered the more reliable despite its validation resting on correlations with the other, less reliable, proxy. Recently, genetic paternity studies have been mooted to provide a potentially superior third measure of sperm competition but so far lack a formal interpretive framework. Here we use the published and relatively comprehensive genetic field studies of the Hominoidea to develop such a framework.
Materials and methods:
Formulae are derived to convert paternity data into a direct measure of the frequency, intensity, and overall level of sperm competition. We then compare these measures with relative testes size at the study, species, and phylogenetic levels.
Results:
A significant correlation between level of sperm competition and relative testes size was obtained at each level. These correlations provide independent support for the continuing use of testes size as a proxy measure when such a measure is sufficient. However, they also suggest that paternity data and our formulae yield a viable alternative measure.
Discussion:
This alternative measure based on paternity data has a number of advantages. Not only is it a potentially direct measure of the level of sperm competition but it also allows the roles of frequency and intensity to be studied separately when of interest.
The purpose of this study is to provide evidence for better guidance related to bed rest after intrauterine insemination (IUI). We conducted a randomized trial to compare the effect of 15 min versus 30 min of bed rest after IUI on pregnancy rate. A total of 204 couples were recruited from May 2021 to December 2021 and randomized to remain in the supine position for either 15 or 30 min after the procedure. The outcomes were the clinical pregnancy rate and comfort level after IUI. Ultimately, 198 couples were included in the analysis. The 15-min immobilization group consisted of 100 couples (226 cycles), and the 30-min immobilization group consisted of 98 couples (225 cycles). The clinical pregnancy rate per couple in the 15-min immobilization group (26 of 100) was not different from that in the 30-min immobilization group (23 of 98). With the use of discrete-time survival analysis, the cumulative probability of clinical pregnancy also showed no difference between these two groups. Based on the literature and on our study, the possible beneficial effect of 30-min immobilization after IUI is at least questionable, and a shorter time could be implemented depending on the results of a systematic review and the individual patient data from the currently executed trials.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
The new edition of this canonical text on male reproductive medicine will cement the book's market-leading position. Practitioners across many specialties - including urologists, gynecologists, reproductive endocrinologists, medical endocrinologists and many in internal medicine and family practice – will see men with suboptimal fertility and reproductive problems. The book provides an excellent source of timely, well-considered information for those training in this young and rapidly evolving field. While several recent books provide targeted 'cookbooks' for those in a male reproductive laboratory, or quick reference for practising generalists, the modern, comprehensive reference providing both a background for male reproductive medicine as well as clinical practice information based on that foundation has been lacking until now. The book has been extensively revised with a particular focus on modern molecular medicine. Appropriate therapeutic interventions are highlighted throughout.
Background
Approximately 40% of human pregnancies are unintended, indicating a need for more acceptable effective contraception methods. New antibody production systems make it possible to manufacture reagent-grade human monoclonal antibodies (mAbs) for clinical use. We used the Nicotiana platform to produce a human antisperm mAb and tested its efficacy for on-demand topical contraception.
Methods
Heavy and light chain variable region DNA sequences of a human IgM antisperm antibody derived from an infertile woman were inserted with human IgG1 constant region sequences into an agrobacterium and transfected into Nicotiana benthamiana. The product, an IgG1 mAb [“Human Contraception Antibody” (HCA)], was purified on Protein A columns, and QC was performed using the LabChip GXII Touch protein characterization system and SEC-HPLC. HCA was tested for antigen specificity by immunofluorescence and western blot assays, antisperm activity by sperm agglutination and complement dependent sperm immobilization assays, and safety in a human vaginal tissue (EpiVaginal™) model.
Findings
HCA was obtained at concentrations ranging from 0.4 to 4 mg/ml and consisted of > 90% IgG monomers. The mAb specifically reacted with a glycan epitope on CD52g, a glycoprotein produced in the male reproductive tract and found in abundance on sperm. HCA potently agglutinated sperm under a variety of relevant physiological conditions at concentrations ≥ 6.25 µg/ml, and mediated complement-dependent sperm immobilization at concentrations ≥ 1 µg/ml. HCA and its immune complexes did not induce inflammation in EpiVaginal™ tissue.
Interpretation
HCA, an IgG1 mAb with potent sperm agglutination and immobilization activity and a good safety profile, is a promising candidate for female contraception.
Multivalent antibodies such as sIgA can crosslink motile entities such as sperm and bacteria, creating agglomerates that are too large to permeate the dense mucin matrix in mucus, a process commonly referred to as immune exclusion. Unfortunately, sIgA remains challenging to produce in large quantities, and easily aggregates, which prevented their use in clinical applications. To develop sIgA-like tetravalent antibodies that are stable and can be easily produced in large quantities, we designed two IgGs possessing 4 identical Fab domains, with the Fabs arranged either in serial or in the diametrically opposite orientation. As a proof-of-concept, we engineered these tetravalent IgG constructs to bind a ubiquitous sperm antigen using a Fab previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG, while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscores the multimerization of IgG as a promising strategy to enhance antibody effector functions based on immune exclusion.
Nowadays, infertility is a problem that affects an increasing number of people. The causes of infertility in a couple may be due to a variety of factors – female, male or unexplained. One of the common problems associated with infertility in women is related to uterine cervical diseases. The cervix is an essential part of the sperm passage, so various disorders in the cervix structure and function may be the cause of infertility. The study aimed to identify the leading cervical causes of female infertility, methods of treatment and their success. The most common problems of cervical origin are cervical polyps and stenosis of the cervical canal. They are easily diagnosed with a routine gynaecological examination and ultrasound examination. Polyps are removed through polypectomy, and after that, a natural pregnancy can be achieved. In the case of stenosis of the cervical canal, there are two treatment options – dilation or intrauterine insemination (IUI). In younger patients and lack of male factor in the couple, dilation is performed. Dilation is mechanical with classic Hegar dilatiors or with synthetic hygroscopic dilatiors (Dilapan). If, in addition to the stenosis of the cervical canal in a woman, there is a male factor, treatment with IUI is preferred. Methods for cervical factor treatment vary in their success rate but are generally characterised by good results.
Fertilization encompasses an exquisitely orchestrated, well‐timed physiological, biophysical, and biochemical series of events. Humans undergo internal fertilization, where the sperm are deposited into the female genital tract. Sperm must then overcome a variety of structural and biochemical obstacles and undergo dynamic changes in order to fulfill their potential. The egg (oocyte) plays more of a passive role, in a physical sense, awaiting the arrival of the sperm. Moreover, there is accumulating evidence that the oocyte–cumulus mass releases a chemoattractant to facilitate sperm attraction towards the oocyte. Following activation, the fertilized oocyte will exit meiotic arrest and undergo mitotic cell division and embryo development. This chapter will review the journey the sperm takes in the female reproductive tract, the biophysical and biochemical changes the sperm must undergo to be able to fertilize the oocyte, and the events of oocyte activation.
Objective:
To assess the extent to which lubricant use during intercourse is associated with time-to-pregnancy (TTP).
Design:
Prospective cohort study.
Setting:
Denmark and North America.
Population:
6,467 women aged 18-49 years who were not using contraception or fertility treatment.
Methods:
We pooled data from two ongoing prospective cohort studies of pregnancy planners in Denmark (2011-2017) and North America (2013-2017). Female participants completed bimonthly questionnaires for 12 months or until reported pregnancy. After restricting to women without a history of infertility who had been trying to conceive for ≤6 cycles at enrollment, 6,467 women were retained for analysis. Self-reported lubricant use was categorized as water-based/not pH balanced, water-based/pH balanced ("fertility friendly"), silicone-based, oil-based, or a combination of these. We used proportional probabilities models to calculate fecundability ratios (FRs) and 95% confidence intervals (CIs) for the association between lubricant use and fecundability after adjusting for cohort and socio-demographic and lifestyle factors.
Main outcome measures:
Fecundability.
Results:
At baseline, 17.5% of participants reported use of lubricants, most commonly water-based/not pH balanced (11.4%). Compared with non-use of lubricants, FRs were 1.02 (95% CI: 0.93-1.11) for water-based/not pH balanced lubricant use, 1.01 (95% CI: 0.86-1.18) for water-based/pH balanced ("fertility friendly") lubricant use, 1.23 (95% CI: 0.94-1.61) for oil-based lubricant use, and 1.27 (95% CI: 0.93-1.73) for silicone-based lubricant use. Associations between oil-based lubricant use and fecundability were inconsistent across subgroups of study cohort, age, parity, and intercourse frequency.
Conclusions:
Lubricant use was not associated with reduced fecundability in the preconception cohorts of pregnancy planners studied This article is protected by copyright. All rights reserved.
Infertility has become a significant problem worldwide. Multiple management options are available
nowadays, which include intrauterine insemination (IUI), in vitro fertilisation (IVF), and intracytoplasmic
sperm injection. IUI is one of the oldest and most popular methods. After >50 years since it was first used,
IUI has evolved through various innovations but still struggles to find its place in infertility management.
After the introduction of revised guidelines from the National Institute for Health and Care
Excellence (NICE) in 2013, there has been a surge in the use of IVF as a primary treatment modality.
The aim of this evidence-based review is to highlight the factors associated with success of IUI and to find
out whether IUI can be offered as a first-line treatment option for infertile couples.
Introduction:
The objective of this systematic review and meta-analysis was to investigate a possible association between immobilization and pregnancy rate in patients undergoing intrauterine insemination.
Material and methods:
To ensure the quality of the methodology, the PRISMA criteria were met at all stages of the development of this meta-analysis. We searched the Cochrane Library, EMBASE, PubMed MEDLINE, ScienceDirect and reference lists of eligible studies from inception to March 2017, without any restriction. We also interviewed the ClinicalTrials.gov database for unpublished articles. Finally, we sought potentially eligible studies in meeting abstracts. Two reviewers independently extracted study characteristics and outcome data. Estimates were pooled using random effects models and sensitivity analyses. We selected studies that compared bed rest to immediate mobilization after intrauterine insemination. The primary outcome was the ongoing pregnancy rate per couple.
Results:
Of 176 identified abstracts, 4 primary studies, all of them randomized controlled trials, met the inclusion criteria, including 1361 couples. The overall relative risk of ongoing pregnancy rate in bed rest versus immediate immobilization was 1.67 95% CI [0.86; 3.22]. The overall relative risk of the live birth rate was 1.11 95% CI [0.56; 2.20].
Conclusion:
This systematic review and meta-analysis was not able to demonstrate that bed rest after intrauterine insemination effectively increases in pregnancy rate. For everyday practice, no specific strategy, bed rest or immediate mobilization, can be recommended at this time.
Male factor is the main cause of infertility in about 20% of infertile couples and contribute to 50% of all cases. Only a limited number of causes of male infertility are potentially treatable and the majority of male infertility is idiopathic. Meta-analyses have shown that empirical medical treatments for unexplained male infertility are merely of unproven benefit. The last decades have witnessed expansion of assisted reproduction techniques (ART) both in terms of advanced technology used and its availability. Intrauterine insemination (IUI) may be considered as a first-line treatment in a couple in which the female partner has a normal fertility status and at least 1 x 106 progressively motile spermatozoa are recovered after sperm preparation. If no pregnancy is achieved after 3–6 IUI cycles of IUI, IVF can be proposed. When less than 0.5 x 106 progressively motile spermatozoa are obtained after seminal fluid processing or sperm are recovered surgically from the testis or epididymis, intracytoplasmic sperm injection (ICSI) should be performed. Although the outcome of no other ART has ever been scrutinized as much before, no large-scale “macroproblems” have as yet been observed after ICSI. ICSI-candidates should be rigorously screened before embarking on treatment and thoroughly informed of the limitations of our knowledge on the hereditary aspects of male infertility and the safety aspects of ART. The vast expansion of especially ICSI treatments demands for global guidelines and inclusion policies for both IVF and ICSI procedures. There is an urgency for improved sperm selection methods and in particular clinical applicability of sperm DNA fragmentation assessment. The medical infertility society should strive towards using the best technology that is available to treat patients in most effective, evidence-based and efficient patient-friendly way.
Twenty-six fertile women who had recent coitus were studied for the presence of uterine sperm at the time of vaginal hysterectomy. The presence of spermatozoa in the uterus correlated directly with high sperm density of the cervical mucus approximately 25-41 hr after coitus. When uterine sperm were present, they were associated with a late proliferative phase endometrium. Sperm degradation occurs in the extracellular fluids of the vaginal cavity and endocervical canal. Phagocytosis of spermatozoa by neutrophils and mononuclear cells occurs in both the vaginal and cervical fluids. © 1970 The American College of Obstetricians and Gynecologists.
Sperm survival in woman
- Rubenstein
The post-coital and post-insemination cervical mucus and semen quality
- MacLeod
Some factors modifying sperm progression
- Schwarz