The role of cine MR imaging in the assessment of uterine function.

PURPOSE: To review the literature on uterine contraction and to highlight magnetic resonance imaging using the cine technique as a useful method to evaluate these movements. METHODS: The literature research on PubMed database was done up to February 2019 with restriction to English language about articles regarding uterine peristalsis and cine MR. RESULTS: Infertility is a common clinical problem and a source of frustration for those who want to have children. Uterine movements are crucial elements in respect of successful conception, implantation, and the development of a healthy pregnancy. It is known that the direction and frequency of uterine peristalsis are closely related to the different phases of the menstrual cycle, and that changes in its activity may interfere with reproduction. One condition that has been linked with infertility by several studies is dysfunctional uterine contractility. Magnetic resonance imaging, using the cine technique, has been shown to be a useful tool in the evaluation of these movements, allowing the identification of patients with some type of dysfunction and establish strategies to increase pregnancy rates. CONCLUSION: Cine MR is an excellent imaging method for the evaluation of uterine peristalsis and identification of dysfunctional contractions.

Evaluation of Uterine Contractility by Magnetic Resonance Imaging in Women Undergoing Embolization of Uterine Fibroids.

PURPOSE: To assess uterine contractility using ultrafast magnetic resonance imaging (cine MRI) before and after uterine fibroid embolization (UFE). MATERIALS AND METHODS: This is a prospective study of uterine contractility in 26 patients (age 30-41 years) undergoing UFE for symptomatic uterine fibroids. Cine MRI was performed before and 6 months after UFE. Two radiologists evaluated uterine contractility and classified it as absent, ordered, or disordered. Patients were then grouped into three distinct patterns of progression: unchanged contractility (group A), modified contractility (B), and loss of contractility (C). These findings were then confronted with factors that might have interfered with uterine contractility pattern (uterine volume, location of dominant fibroid, fibroid/myometrium index, and fibroid necrosis pattern). RESULTS: Of the 26 patients, 8 (30.7%) had no contractility before the procedure, while 18 (69.2%) exhibited some form of contractility (11 [61%] ordered, 7 [39%] disordered). All 8 patients who had no contractility at baseline exhibited contractility after UFE (5 ordered, 3 disordered). Of the 11 who had ordered contractility at baseline, 9 remained ordered and 2 lost contractility after UFE. Of the 7 with disordered contractility at baseline, 1 remained disordered, 5 progressed to ordered contractility, and 1 lost contractility. Overall, 10 patients (38%) had no change in contractility after UFE (group A), 13 (50%) had a positive change (group B), and 3 (11%) lost contractility (group C). The potential interference factors assessed had no statistically significant effect in any group. CONCLUSION: In women of reproductive age with symptomatic fibroids, uterine contractility improved significantly after UFE. LEVEL OF EVIDENCE: Level 3-non-randomized controlled cohort/follow-up study.

Functional magnetic resonance imaging for clinical evaluation of uterine contractility / Ressonância magnética funcional para avaliação clínica da contratilidade uterina

ABSTRACT Uterine contractility out of the gestational phase, during the menstrual cycle and the habitual functional variations of the organ, this is one of the responsible mechanisms for reproduction and fertility, due to its direct action in the mechanisms conducting the spermatozoa to the ovule and in the decidual implantation. Pathologies such as uterine leiomyoma, endometriosis, adenomyosis, polycystic ovarian syndrome, as well as the use of intrauterine devices and oral contraceptives, may alter a functionality of uterine contractility. Thus, magnetic resonance imaging with ultrafast sequences provides a dynamic evaluation (cine-MRI) and thus the correlation of uterine contractility quality in patients with current infertility or pathologies.

RESUMO A contratilidade uterina fora da fase gestacional, durante o ciclo menstrual e as habituais variações funcionais do órgão, é um dos mecanismos responsáveis pela reprodução e fertilidade, devido sua ação direta nos mecanismos de condução dos espermatozoides até o óvulo e na implantação decidual. Patologias como leiomioma uterino, endometriose, adenomiose, síndrome dos ovários policísticos, bem como o uso de dispositivos intrauterinos e anticoncepcionais orais, podem alterar a funcionalidade da contratilidade uterina. Desta forma a ressonância magnética com sequências ultra-rápidas proporcionam uma avaliação dinâmica (cine-RM) e assim a correlação da qualidade da contratilidade uterina em pacientes com infertilidade ou patologias vigentes.

Insights into the role of cervical mucus and vaginal pH in unexplained infertility / Sobre o papel do muco cervical e do PH vaginal na gênese da infertilidade inexplicada

Unexplained infertility diagnosis is made in the presence of a normal semen analysis when tubal patency and normal ovulatory function are established. Among several potential causes, unexplained infertility could be attributed to vaginal pH and cervical mucus abnormalities. Although the vaginal canal and the cervix generally function as effective barriers to sperm, and although the production of mucus is essential to transport them from the vagina to the uterine cavity, these factors receive little attention in the investigation of couples with unexplained infertility. A substantial reduction in sperm number occurs as they transverse the cervix. From an average of 200 to 300 million sperm deposited in the vagina, only a few hundred achieve proximity to the oocyte. Given this expected high spermatozoa loss, a slight modification in cervical mucus may rapidly transform the cervix into a "hostile" environment, which, together with changes in vaginal environment and cervix structure, may prevent natural conception and be a cause of infertility. In this review, we discuss the physiological role of the vaginal pH and cervical mucus in fertility, and describe several conditions that can render the cervical mucus hostile to sperm and therefore be implicated in the pathophysiology of unexplained infertility.

RESUMO O diagnóstico de infertilidade inexplicada baseia-se na presença de espermograma normal, constatadas também permeabilidade tubária e função ovulatória normais. Entre as várias causas potenciais de infertilidade inexplicada, a presença de muco cervical e pH vaginal anormais devem ser consideradas. Embora a produção adequada de muco cervical seja essencial para o transporte dos espermatozóides da vagina para a cavidade uterina, e tanto o canal vaginal quanto o colo do útero desempenham função importante como barreira à passagem dos espermatozóides, estes fatores recebem pouca atenção na investigação de casais com infertilidade inexplicada. Uma redução substancial do número de espermatozoides ocorre à medida que estes percorrem o trato reprodutivo feminino. Partindo de cerca de 200 a 300 milhões de espermatozoides depositados na vagina, apenas algumas centenas alcançam a proximidade do oócito. Alteracões do muco cervical podem rapidamente transformar o colo do útero num ambiente hostil, que em conjunto com alterações no ambiente vaginal e da estrutura de colo do útero, podem apresentar-se condicões impedientes para a concepção natural; desse modo, convertem-se em causa de infertilidade. Nesta revisão, discutimos o papel fisiológico do pH vaginal e do muco cervical na fertilidade, descrever várias condicões que podem tornar o muco cervical hostil aos espermatozoides e, por fim analisamos como estes fatores interferem na fisiopatologia da infertilidade inexplicada.

Transporte espermático na égua / Sperm transport in the mare

O objetivo deste trabalho foi realizar uma revisão bibliográfica sobre o transporte espermático na égua. Um rápido transporte espermático ocorre logo após a inseminação artificial (IA), sendo que a presença de espermatozoides na ponta dos cornos uterinos é observada oito minutos após esta. Espermatozoides podem ser observados 30 minutos após a IA e permanecer nas tubas uterinas por pelo menos 24 horas. Verificou-se que os espermatozoides podem ser observados em 62,6% das éguas quando se usa microscopia de luz, tanto nas glândulas uterinas como no epitélio do útero. Glândulas uterinas podem atuar como um reservatório de espermatozoides. O número de éguas com espermatozoides no epitélio uterino, nas glândulas e na junção útero-tubárica diminui em relação ao tempo após a IA.(AU)

The objective of this study was to review the literature on sperm transport in the mare. A rapid sperm transport occurs soon after artificial insemination (AI), and the presence of sperm on the tip of the uterine horns is observed after eight minutes. Sperm can be observed 30 minutes after AI and remain in the uterine tubes for at least 24 hours. It was found that the sperm can be observed in 62.6% of the mares when using light microscopy, both in the uterine glands and the epithelium of the uterus. Uterine glands may act as a reservoir for sperm. The number of mares with spermatozoa in the uterine epithelium, glands, and utero-tubal junction decreases over time after AI.(AU)

Transporte espermático na égua / Sperm transport in the mare

O objetivo deste trabalho foi realizar uma revisão bibliográfica sobre o transporte espermático na égua. Um rápido transporte espermático ocorre logo após a inseminação artificial (IA), sendo que a presença de espermatozoides na ponta dos cornos uterinos é observada oito minutos após esta. Espermatozoides podem ser observados 30 minutos após a IA e permanecer nas tubas uterinas por pelo menos 24 horas. Verificou-se que os espermatozoides podem ser observados em 62,6% das éguas quando se usa microscopia de luz, tanto nas glândulas uterinas como no epitélio do útero. Glândulas uterinas podem atuar como um reservatório de espermatozoides. O número de éguas com espermatozoides no epitélio uterino, nas glândulas e na junção útero-tubárica diminui em relação ao tempo após a IA.

The objective of this study was to review the literature on sperm transport in the mare. A rapid sperm transport occurs soon after artificial insemination (AI), and the presence of sperm on the tip of the uterine horns is observed after eight minutes. Sperm can be observed 30 minutes after AI and remain in the uterine tubes for at least 24 hours. It was found that the sperm can be observed in 62.6% of the mares when using light microscopy, both in the uterine glands and the epithelium of the uterus. Uterine glands may act as a reservoir for sperm. The number of mares with spermatozoa in the uterine epithelium, glands, and utero-tubal junction decreases over time after AI.

Timing of onset of contraceptive effectiveness in Depo-Provera users: Part I. Changes in cervical mucus.

OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.

PIP: More accurate knowledge of the time of onset of cervical mucus changes after Depo-Provera injection would enable family planning providers to counsel new acceptors to use a backup method only for the amount of time it is really needed. To obtain such data, 30 women from a family planning clinic in Campinas, Brazil, who requested Depo-Provera in 1995-96 were recruited. At baseline, 11 women had a poor cervical mucus score (0-4), 12 had a fair score (3-8), and 7 scored in the good range (9-12). Between 6 and 24 hours after injection, a sharp decline occurred in the cervical mucus score in all but 3 patients (each of whom had a "good" score at baseline). On day 3, 29 women had "poor" mucus and the remaining woman had a cervical mucus score in the fair range. By day 7, 29 women had zero mucus scores; the score in the last woman was 1. 24 hours after injection, sperm penetration (measured by vanguard sperm distance) had decreased to under 1 cm in all but 4 women. At day 3, 1 of the 2 women with good penetration at 24 hours maintained a vanguard sperm distance of 2.5 cm and an estimated sperm count of 15,363. By day 7, sperm penetration was zero in all but 1 woman (0.5 cm). These findings confirm that depot medroxyprogesterone acetate causes profound changes in cervical mucus after injection. The lack of a more complete hostility to sperm penetration at day 3 was unexpected, however. Given the nonavailability of a reliable clinical marker to verify a contraceptive effect at 3 days, it seems prudent to advise new Depo-Provera acceptors to use a backup method for the first 7 days.

Temporal relationship between Uniplant insertion and changes in cervical mucus.

This study was undertaken to determine the time required by a single implant containing nomegestrol acetate to affect cervical mucus production and sperm penetration in women. All subjects were investigated and, if necessary, treated for any kind of cervicitis or vaginitis prior to starting cervical mucus study. The subjects had not used hormonal contraception for at least three months prior to investigation. They were counseled to use condoms during this study and also to refrain from intercourse during the period of cervical mucus sampling. Follicular development and endometrial thickness were analyzed by transvaginal sonography. Cervical mucus examination, sperm penetration test, and transvaginal sonography were performed during the control cycle and during the first cycle of Uniplant use. Blood samples were taken for the measurement of estradiol, LH, and progesterone. Cervical mucus and sperm penetration tests were evaluated according to the World Health Organization (WHO) criteria. In the treated cycle, when cervical mucus reached a score of 8-10, Uniplant was inserted, independent of the day of the cycle. Cervical mucus was then collected at 0, 4, 8, 12, 24, 48, and 96 h later until a marked change in volume, consistency, ferning spinnbarkheit, and cellularity was observed. All samples were also used for sperm penetration test. Preovulatory estradiol and LH peak decreased significantly compared to pre-implant insertion. Progesterone levels were within the normal limit. Cervical mucus and sperm penetration tests were not affected by Uniplant in the first 12 h. Twenty-four hours after Uniplant insertion, cervical mucus and sperm penetration tests were affected in 70.6% of the women. Forty-eight hours after implant insertion, the women were affected. Follicular rupture occurred in the majority of the women 48 h after implant insertion. Based on these results, it is possible to conclude that Uniplant can affect estradiol and LH preovulatory peaks and disrupt the process of cervical mucus production and sperm penetration, but it was unable to prevent ovulation when inserted in the preovulatory phase.

PIP: In Brazil, physicians inserted one single capsule of the nomegestrol acetate contraceptive implant (Uniplant) subcutaneously in the gluteal region of 17 healthy female volunteers (mean age = 24.62 years) when their cervical mucus score was 8-10. They performed cervical mucus examination, sperm penetration test, and transvaginal sonography during the control cycle and during the first cycle of Uniplant use. They took blood samples to measure estradiol, luteinizing hormone (LH), and progesterone. Uniplant contained 55 mg of nomegestrol acetate. The researchers aimed to determine the time between Uniplant insertion and changes in cervical mucus and in the ability of sperm to exhibit forward motility in the cervical mucus. When Uniplant was inserted in the early follicular phase, the preovulatory peaks of estradiol and LH were significantly lower than preinsertion peaks (539.4 vs. 1087.1 pmol/l and 12 vs. 40.4 IU/l, respectively; p 0.01). The lower progesterone levels in the treatment cycle were not significantly different than preinsertion progesterone levels (46.6 vs. 53.8 nmol/l; p = 0.055). Ultrasonography and progesterone levels indicated that 16 of the 17 treatment cycles were ovulatory. Neither cervical mucus nor sperm penetration was affected in the first 12 hours postinsertion. By 24 hours postinsertion, 70.6% of the women exhibited significant changes in both cervical mucus and sperm penetration. At the end of 48 hours, all 17 women had these changes. These findings suggest that Uniplant inserted in the periovulatory phase affects cervical mucus production, sperm penetration, and preovulatory peaks of LH and estradiol but does not affect ovulation.

Inactivation of SH groups with sesquiterpene lactones: effects on nuclear decondensation pattern / motility induced by heparin in human spermatozoa.

PIP: In Guadalajara and Mexico City, Mexico, researchers collected and analyzed semen samples from fertile men who were sexually abstinent for 3 days to evaluate the effect heparin has on sperm nuclear decondensation patterns and motility. They used 3 sesquiterpene-lactones to inactivate the thiol groups on the outer membrane of sperm cells: I (17, 18 dehydroviguiepinin), II (Budlein A), and III (Zaluzanin A). Sesquiterpene-lactones I, II, an III had an inhibitory effect of 81%, 73%, and 27%, respectively, 6 hours after the sperm had been incubated with heparin for 6 hours. First mixing the sperm with reduced glutathione before adding 17, 18 dehydroviguiepinin increased the decondensating effect of heparin 350% above that of sperm not incubated with both glutathione and heparin. Sperm motility fell 80%, 60%, and 16%, respectively, 15 minutes after incubation with sesquiterpene-lactones I, II, and III. When sperm was incubated with heparin only, sperm motility was consistently higher for 5 hours. None of the compounds used to incubate the sperm affected sperm viability. The findings provided more information about the molecular biology of mammalian spermatozoa and suggested that sesquiterpene-lactones may be effective male contraceptives.^ieng

Clinical experience with gossypol in non-Chinese men: a follow-up.

Gossypol monoacetic acid was administered to 12 Brazilian volunteers. The initial dose was 20 mg daily for 4 months. The dose was then reduced to 60 mg weekly (20 mg three times weekly). A significant reduction in sperm motility was detected in all subjects. An increase in the number of immature cells in the ejaculate was also detected in all subjects. Severe oligospermia or azoospermia developed in all subjects at the end of the loading phase. Two years following discontinuation, 3 men were still azoospermic. Only 1 man who was azoospermic 2 years after discontinuation had a late (3 years) recovery. Two of the 3 men who were subjected to high spermatic vein ligation because of varicocele remained azoospermic 2 years after the operation. The third patient, who did not have the operation, also remained azoospermic. Of the 9 patients who recovered, 3 had fathered children during the last 2 years.

The mode of action of IUDs.

In women, IUDs produce alterations of the uterine environment in terms of a pronounced foreign body reaction. This biological response may interfere with steps of the reproductive process that normally take place before the ovum reaches the uterine cavity. In order to discuss this hypothesis on the mechanism of action of IUDs, this review is focussed on 1) detection in urine and blood of substances alleged to be specifically produced by the embryo, 2) migration of gametes in the female genital tract, and 3) microscopic features of ova recovered from the genital tract.

PIP: This review delves into the mode of action of IUDs in greater detail than the commonly held theory that IUDs prevent implantation: it discusses whether IUDs affect fertilization, gamete migration or development of fertilized ova. In order to determine whether IUDs prevent fertilization, noninvasive methods of detecting fertilization, or very early pregnancy tests, would be necessary. Two approaches are to assay an alleged immunosuppressive early pregnancy factor, and to design extremely sensitive assays for trophoblastic gonadotrophin (hCG). In fertile cycles, such studies found a 6 to 57% incidence of fertilized ova that did not result in pregnancy. Comparable studies in IUD users sought a transient rise in hCG. Some researchers have seen a fleeting hCG with standard assays, but one laboratory using a new immunoradiometric assay found hCG in only 0.9% of cycles in IUD users. Following sperm or egg migration in women is possible by flushing the vagina and endocervix, or the tubes during surgery. Normally sperm can reach the oviduct in 2 hours and remain viable as long as 85 hours. With an IUD in place, several searches recovered no sperm in the tubes, presumably they were phagocytosed. Copper IUDs especially reduced numbers of sperm, and those found often had heads decapitated from tails. Ovum migration in IUD wearers was not appreciably affected through the oviduct, but few eggs were found in the uterus, again far fewer were found in copper IUD users. Looking at ova that were detected in IUD users, none were developing normally, the rest were classified as either abnormal or uncertain. Ova from copper IUD users were distinctive for being without vitellus and surrounded by macrophages. This preliminary research as a whole suggests that IUDs affect events prior to implantation, specifically ovum development in the tubes, sperm migration, and ovum transport in the uterus.

[The history of research on contraceptive methods in the Dominican Republic]. / Historia de la investigacion sobre metodos anticonceptivos en RD.

PIP: The Center for Investigation and Services in Human Reproduction and Contraception (CINSERHA), under the auspices of the Dominican association for Family Welfare (PROFAMILIA), conducts research in human reproduction and on the efficacy, effectiveness, seconardy effects, and other characteristics of contraceptive methods, as well as providing family planning services to more than 15,000 women each year. CINSERHA's research activities began in 1974 and have primarily involved development of Norplant subcutaneous implants, vaginal contraceptive rings, different models of IUDs, and male injectable methods. The most significant results to date have been contributions to the successful development and acceptance of the Norplant system, proff that IUDs do not entail "microabortions", and demonstration that the periovulatory period is the time of optimal conditions for sperm migration in the female genital tract. The objectives of CINSERHA studies are to develop new contraceptive methods, to achieve a better understanding of female physiology, and to explain the mechanisms of action of current contraceptive methods. CINSERHA participates in collaborative international studies with the US, Finland, Sweden, Chile, Brazil, and Jamaica under the leadership of the Population Council. 400 implants have been placed over 9 years and only 2 pregnancies have occurred, giving a failure rate of .4. The only side effect has been menstrual irregularity, which has tended to clear up with time. The only male method studied was a monthly injection of medroxyprogesterone and testosterone, which was abandoned as unpromising after 2 years of study. The cottonseed extract gossypol may be studied in the future, and studies on the vaginal ring have been successful except that some women complained of excessive vaginal discharge.^ieng

[Mechanism of action of prolonged-action injectable contraceptives]. / Mecanismo de accion de los contraceptivos inyectables de deposito.

PIP: Several parameters were studied to clarify the mechanisms of action of 2 prolonged-action injectable contraceptives: 17alpha-19-hydroxynorprogesterone caproate (with a contraceptive effectiveness of at least 8 weeks) and 19-norethindrone enanthate (effectiveness over 12 weeks). The generally accepted theory of ovulation inhibition was unconvincing. In 14 ovarian biopsies of patients under treatment, taken in the 2nd phase of the cycle, ovulation was evidenced in 11 cases by the presence of corpora lutea. 245 endometrial biopsies showed that the exogenous gestagen effect lasts only 3 weeks; after such period, most endometria could be correlated with the day of the cycle on which they were taken; 2/3 of them suggested biphasic cycles. An evaluation of 240 colpocytograms also confirmed endogenous cyclic activity. In order to explain the prolonged contraceptive effectiveness of the drugs, the cervical mucus was thoroughly studied in 380 cases. A definite, uniform, and constant effect of the progestogen on the mucus was demonstrated, in contrast to the cyclic changes in the other parameters; such effect begins to decline simultaneously with the loss of contraceptive protection. It is suggested that the effectiveness of the 2 drugs is due to changes in the cervical mucus, which affect sperm penetration.^ieng