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Ministerial Directive No. 1072, June 1985.

This Directive contains nonmandatory guidelines and recommendations for in vitro fertilization and embryo transfer in Chile. The Guidelines are based on the assumption that the constitutional guarantee of the right of the child to be born includes the right to procreate. They set forth the medical reasons for the use of these assisted reproduction techniques, procedures to be followed by institutions applying these techniques, technical facilities, qualifications of medical staff, and the manner in which records are kept. They recommend the mandatory appointment of an Ethics Committee and the obligation to advise couples using these techniques. They also recommend the requirement that all normal and fertilized ovules be returned to the mother and not stored or used for research.

Americas↗

Luteal phase support.

Assisted reproductive techniques have become a routine treatment for infertility. The extended use of gonadotrophin-releasing hormone analogues in assisted reproductive techniques has made luteal phase support mandatory, as it has been clearly demonstrated that they alter luteal LH pulsatility. For luteal support, HCG administration, though effective, has a high risk of ovarian hyperstimulation syndrome. Progesterone continues to be the gold standard for supplementation. Vaginal progesterone represents a highly effective alternative to painful intramuscular injections. The vaginal route is mainly characterized by direct delivery of the progesterone to the endometrium, thus producing high levels at the target tissue and a very low incidence of side effects.

Journal Article↗

Ovarian control for assisted reproduction in the domestic cat and wild felids.

Of the 37 felid species, all but the domestic cat are classified as threatened with extinction in all or part of their native range. Additionally, the domestic cat is a valuable model for human biomedical research. Propagating some wild felids as well as domestic cat populations serving as human models is a major challenge primarily due to difficulties in transporting animals between facilities to ensure the pairing of genetically matched individuals, behavioral incompatibility between pairs and low fertility. Artificial insemination (AI) and in vitro fertilization/embryo transfer (IVF/ET) are powerful tools for helping manage rare populations. Developing successful assisted reproductive techniques requires knowledge of the female reproductive cycle and precise control of ovarian activity. Successful ovarian stimulation for AI and IVF/ET has been achieved in at least one-third of all cat species. However, sensitivity to a given gonadotropin treatment appears highly species-specific, and poor responses are common, particularly in felid species that exhibit spontaneous ovulations. Furthermore, current gonadotropin regimens have been demonstrated to perturb female reproductive function often leading to reduced fertility. Overall, ovarian response to exogenous hormonal stimulation has been highly variable, and pregnancy success after AI or IVF/ET remains low (<20%) in most species. Therefore, there is an immediate need to develop improved regimens that would allow more predictable ovarian responses in felids. We contend that recent research involving the use of progestins to control the ovary prior to gonadotropin stimulation shows promise for providing consistent ovarian stimulation in felids.

Animals↗

Generation of normal progeny by intracytoplasmic sperm injection following grafting of testicular tissue from cloned mice that died postnatally.

Animal cloning by nuclear transfer has been successful in several species and was expected to become an alternative reproductive technique. Among the problems associated with this cloning technique, however, are its low success rate and high mortality of cloned animals even if they develop to term. Nuclear transfer has thus come to be considered too difficult to apply as a reproductive technique. The transplantation of male germ cells or pieces of testicular tissue has enabled the induction of spermatogenesis from fetal or postnatal male mice. In the present study, we examined whether functional male gametes could be obtained by the transplantation of pieces of testicular tissue from cloned mice that died immediately after birth with typical aberrant phenotypes, such as large offspring syndrome. Donor testicular tissues were retrieved from cloned mice that died postnatally and were transplanted into the testes of recipient nude mice. Two to three months after transplantation, the grafted donor testicular tissue had grown in the host testis, and histological analysis showed that spermatogenesis occurred within the graft. Intracytoplasmic sperm injection demonstrated that the testicular sperm generated in the grafted donor tissue were able to support full-term development of progeny. These results clearly showed that functional spermatogenesis could be induced by transplanting testicular tissue from cloned mice that died postnatally into recipient mice. The strategy presented here will be applicable to cloned animals of other species, because the xenografting of testicular tissue into mice has been demonstrated previously to be possible.

Animals↗

Results in the United States with sperm microaspiration retrieval techniques and assisted reproductive technologies. The Sperm Microaspiration Retrieval Techniques Study Group.

Improved methods of urological microsurgery and of various assisted reproductive technologies have resulted in the ability to achieve pregnancies with sperm aspirated microsurgically from men with bilateral congenital absence of the vasa deferentia or with ductal obstructions that cannot be surgically reconstructed. A survey was conducted of the results of such procedures performed in the United States during approximately 2 years. Female partner ovarian stimulation was initiated in 219 instances at 22 centers. Of the 219 procedures 23 (11%) were terminated without attempting any form of gamete fertilization or insemination of the wife for various reasons (no sperm or too few sperm retrieved, poor to absent sperm motility or poor quality eggs). The etiology of azoospermia in the 219 procedures was congenital absence of the vasa deferentia in 115 cases (52%), other congenital conditions in 15 (7%), failed vasectomy reversal in 37 (17%), infection in 4 (2%), other conditions (mainly ejaculatory dysfunctions that did not respond to electroejaculation and complex ductal obstructions) in 26 (12%) and not specified in 22 (10%). When only patient sperm was used pregnancy was achieved in 12 of 115 wives (10%) of those men who had congenital absence of the vasa deferentia and in 0 to 14% of the wives of men whose azoospermia was caused by other conditions. Of the 219 menstrual cycles in which ovarian stimulation was initiated pregnancy occurred in 24 (11%) with patient sperm and in 9 (4%) with donor sperm. Of these 33 pregnancies a full-term, live delivery occurred in 17 (52%), while 8 (24%) were ongoing at the time of reporting, 2 (6%) miscarried, 3 (9%) were chemical pregnancies, 1 (3%) resulted in a stillborn child and the outcome was unknown in 2 (6%). This new therapy offers only a modest chance of pregnancy. However, it affords men with azoospermia the opportunity to achieve paternity with their own sperm when other therapies are not available or applicable.

Epididymis↗

Comparative study of perinatal outcome of dichorionic and trichorionic iatrogenic triplets.

OBJECTIVE: The purpose of this study was to compare the perinatal outcome of dichorionic and trichorionic triplets who were conceived by assisted reproductive techniques. STUDY DESIGN: In this retrospective study, the maternal, neonatal, and chorionicity data were collected from 106 sets of trichorionic triamniotic and 34 sets of dichorionic triamniotic triplet pregnancies who were conceived by assisted reproductive techniques between January 1986 and December 2000. Perinatal and neonatal data were evaluated in relation to chorionicity and intertriplet birth weight discordance. RESULTS: The dichorionic triamniotic triplets have an 8-fold higher risk of perinatal death than trichorionic triamniotic gestations (odds ratio, 7.9; 95% CI, 4.4-14.0; P < .001). This is attributed to a higher risk of very low birth weight (P < .01), delivery at < 30 weeks of gestation (P < .001), and premature rupture of membrane (P < .001) in dichorionic triamniotic triplets compared with trichorionic triamniotic pregnancies. Twin-twin transfusion syndrome (odds ratio, 11.5; 95% CI, 4.8-27.7; P < .001), delivery at < 30 weeks of gestation (odds ratio, 40.5; 95% CI, 16.9-97; P < .01), premature rupture of membrane (odds ratio, 6.7; 95% CI, 3.8-11.9; P < .01), and nulliparity (odds ratio, 3.1; 95% CI, 1.6-6.1; P < .05) had independent effects on perinatal loss rate. CONCLUSION: The dichorionic triplets have an 8 times higher perinatal mortality rate than trichorionic triamniotic pregnancies.

Adult↗

Cause and risk of stillbirth in twin pregnancies: a retrospective audit.

BACKGROUND: The epidemiology of twin pregnancies complicated by stillbirth of one or both fetuses is a scarcely examined area. The risk of perinatal death in twin pregnancies is increased 2-5 times compared to singletons, and the identification of preventable risk factors becomes increasingly important as the number of multiple pregnancies is rising. We report the causes of death in twin pregnancies and their respective risk factors. METHODS: Twin pregnancies (n = 54) complicated by antepartum or intrapartum stillbirth of one or both twins (n = 68) and twin pregnancies with normal outcome (n = 103) in the counties of Oslo and Akershus, Norway, from 1986 to 1995 were included. The cases were classified and compared to the controls in multiple logistic regression analyses with regard to risk factors. RESULTS: The risk of stillbirth increased with monochorionicity, non-Western origin and assisted reproduction techniques (ART). The cases could be divided into eight different groups according to the primary diagnosis. The groups did not fit any of the existing cause-of-death classifications used on singleton stillbirths. CONCLUSIONS: The identification of monochorionic gestation should be made early in pregnancy to designate the level of risk. Assisted reproduction techniques leading to a high incidence of twins should be avoided. Health care professionals in the immigrant population should address the detrimental effects of consanguinity on reproductive outcome. We emphasize the need of a new cause-of-death classification for twin stillbirths.

Case-Control Studies↗

Sperm cryopreservation for men with nonmalignant, systemic diseases: a descriptive study.

Cytotoxic drugs and immunosuppressive therapies are used to treat patients with nonmalignant, nontesticular systemic diseases. These therapies can permanently suppress spermatogenesis. Sperm cryopreservation before treatment theoretically could give these men the opportunity to achieve a pregnancy with a woman later in life when the couple decides to do so. However, it is not known whether pretreatment sperm quality in these men is good enough to be used for assisted reproductive techniques. The main objective of this study was to determine the usefulness of cryopreservation in this patient population by: 1) assessing their pretreatment semen quality (eg, count, motility, and motion kinetics) and comparing it with that of healthy donors before and after cryopreservation; 2) comparing patients' pretreatment semen characteristics with World Health Organization reference values for normal sperm; and 3) examining the differences in semen parameters among patient groups. Semen specimens were obtained from 25 healthy donors and from 23 patients with a variety of disorders (12 had autoimmune disorders, 4 had kidney disorders, 3 had diabetes, 2 had ulcerative colitis, and 2 had heart transplants). All patients, except those with diabetes, required immunosuppressive or cytotoxic therapy. Although the pretreatment quality of the semen of these patients was not as good as that of donors, semen samples were within the normal reference range of the World Health Organization. No statistically significant differences in sperm parameters were found within the 4 patient groups except for those with diabetes (n = 3), who showed poorer sperm counts (P < .04). However, no conclusive evidence can be reached due to the small sample size. Our results indicate that pretreatment semen quality in these patients is adequate for reproductive techniques. We believe that cryopreservation should be offered to patients of reproductive age with disease or treatment regimens that may cause infertility.

Adult↗

New techniques for reproduction of the condyle relation and reduction of complications after sagittal ramus split osteotomy of the mandible.

One hundred three patients underwent a modified sagittal ramus split osteotomy of the mandible. Maintenance of the temporomandibular joint relationship prior to the procedure was achieved postoperatively by using a three-dimensionally adaptable fixation bar. Techniques were also developed to avoid damage to the inferior alveolar nerve during the osteotomy and application of lag screws. These procedures avoided the disadvantages of lag screw osteosynthesis, and reduced relapse.

Bone Screws↗

Genomic imprinting and assisted reproduction.

Imprinted genes exhibit a parent-of-origin specific pattern of expression. Such genes have been shown to be targets of molecular defects in particular genetic syndromes such as Beckwith-Wiedemann and Angelman syndromes. Recent reports have raised concern about the possibility that assisted reproduction techniques, such as in vitro fertilization or intracytoplasmic sperm injection, might cause genomic imprinting disorders. The number of reported cases of those disorders is still too small to draw firm conclusions and the safety of these widely used assisted reproduction techniques needs to be further evaluated.

Journal Article↗

[Analysis of risk factors for ectopic pregnancy in own material in the years 1993-2002].

UNLABELLED: The ectopic pregnancy is still a life-threatening condition. The risk factors for ectopic pregnancy are divided into four groups: 1) mechanic factors, 2) tubal dysfunction, 3) assisted reproductive techniques (ART) and 4) hormonal factors. MATERIAL AND METHODS: On basis of the analysis of medical documentation we determined the risk factors for ectopic pregnancy in 214 patients (aged 18-44, mean 32 +/- 9 years) hospitalized in Department of Reproductive Medicine and Gynecology of Pomeranian Medical University between 1993 and 2002. The control group composed 215 patients admitted to the hospital outpatient clinic in the years 1993-2002. RESULTS: The risk factors for ectopic pregnancy evaluated in each group of patients were: history of adnexitis, surgical procedures (appendectomy, tubal microsurgery, ovarian cystectomy, adnexectomy, myomectomy, cesarean section, previous conservative surgical treatment of ectopic pregnancy, salpingectomy), appendicitis complicated by peritonitis, endometriosis, conservative treatment of ectopic pregnancy, insertion of IUD, ovarian induction or IVF procedure, uterine defects and smoking. In the examined group 104 patients had a history of surgery (48.5%) compare to 40 patients in the control group (18.6%). Difference between groups is significant p = 0,034. In 40 cases out of 104 (18.6%) surgical operations were done two and more times. Statistics proves that surgical procedures in the past occurred significantly more frequently in the studied than in control group. The most frequent operations were: conservative surgical treatment of ectopic pregnancy (p = 0.000), tubal microsurgery (p = 0.0016), ovarian cystectomy (p = 0.013) and salpingectomy (p = 0.047). Appendectomies or myomectomies in the past did not increase the risk of ectopic pregnancy. Additionally, in the examined group there were more cases of MTX (Methotrexate) therapy applied in the past because of ectopic pregnancy (p = 0.000), more smoking (p = 0.0001) and more adnexitis in the past (p = 0.013). Treated endometriosis in the past, artificial reproductive techniques (ART), peritonitis, IUD application and uterine defects were no important risk factors for ectopic pregnancy. CONCLUSIONS: The main risk factors for ectopic pregnancy are: history of surgical procedures, especially conservative surgical treatment of ectopic pregnancy and tubal microsurgery. Appendectomy or myomectomy do not increase this risk. The other important risk factors for ectopic pregnancy are: conservative treatment of ectopic pregnancy in the past and smoking. Adnexitis is another risk factor for ectopic pregnancy.

Adult↗

Management strategies for male factor infertility.

Although modern assisted reproduction techniques contribute a lot to overcoming severe male factor infertility, application of these methods in every infertile couple would represent an over-treatment. Therefore, conventional treatment modalities are still the first approach to male fertility disorders. Apart from assisted reproduction techniques, these include surgical procedures and the administration of drugs. Causal treatment regimens of proven effectiveness are only available for patients with infertility resulting from hypogonadotrophic hypogonadism. Drug treatment of retrograde ejaculation is also effective. Inconsistent results have been obtained with empirical treatment including antiestrogens, androgens, aromatase-inhibitors, mast cell blockers, zinc and pentoxifylline. Anti-inflammatory and immunosuppressive therapy as well as treatment with antioxidants in the presence of reactive oxygen species has not yet been demonstrated to be effective by controlled studies but represent at least a rational approach which should be investigated more thoroughly. High dosage administration of follicle stimulating hormone aimed particularly at improving disturbed sperm structures, and the combination of tamoxifen with androgens, may be promising developments. A careful diagnostic work-up is necessary before any andrological treatment is commenced so that adequate treatment options can be selected for individual patients.

Adrenal Cortex Hormones↗

The role of luteinizing hormone in folliculogenesis and ovulation induction.

OBJECTIVE: To review the physiologic, pathophysiologic, and clinical roles of LH in follicle and oocyte development and maturation and to assess the effects of LH content in exogenous gonadotropin preparations used for ovulation induction. DESIGN: Critical review of the scientific literature devoted to folliculogenesis. Evaluation of comparison studies that used different gonadotropin preparations for ovulation induction. CONCLUSION(S): Folliculogenesis and oocyte maturation are complex processes that require the action of both LH and FSH. Luteinizing hormone is essential to provide the androgen substrate for estrogen synthesis, which in turn contributes to oocyte maturation and may play a relevant role in optimizing fertilization and embryo quality. Although the excessive LH secretion that is present in some disorders is detrimental to reproductive function, this is not applicable to ovulation induction with hMG because this menotropin does not increase daily plasma LH levels. The results of ovulation induction with hMG or FSH-only regimens did not differ in studies conducted in patients with polycystic ovary syndrome and in most studies conducted in ovulatory women undergoing assisted reproductive techniques; conversely, hMG was clearly superior to purified FSH for the treatment of hypogonadotropic hypogonadism. Miscarriage rates were not affected by the use of hMG. Thus, low but detectable LH concentrations positively influence the outcome of ovulation induction in patients with ovulatory disorders and women undergoing assisted reproductive techniques.

Estrogens↗

[Congenital malformations in children born after IVF].

BACKGROUND: Major congenital malformations are a leading cause of perinatal morbidity and mortality. Congenital malformations are caused by three factors: genetic, environmental or multifactorial, all of which are present in the context of artificial reproductive techniques. FINDINGS: In 1999 Bergh et al. conducted a retrospective study, which included all the children born following IVF treatment in Sweden. The relative risk found was RR = 1.39 [95% CI 1.25-1.54] and there was no stratification for maternal age and parity. In 2002 Hansen et al. conducted a well-established retrospective study in Western Australia. When only term singletons were included in the study, the OR found was OR = 2.1 [1.4-3.2] in the IVF group and OR = 2.2 [1.2-4] in the ICSI group. Results were stratified for maternal age, parity and offspring sex. A meta-analysis of 19 studies found a relative risk of 1.29 for major malformations among IVF pregnancies. DISCUSSION: Explanations for the increased risk of fetal malformations could be divided into three categories: first, the characteristics of the infertile population which include many risk factors: older age, lower parity, chronic diseases and infertility itself. Second, the techniques used to treat infertility are not physiologic. Third, the characteristics of the pregnancy achieved: the incidence of high-order pregnancies is much greater and this fact exposes the offspring to other risk factors such as preterm birth and low birth weight. CONCLUSIONS: Major advances in reproductive techniques offered hope for many couples, but they were also the reason for much concern regarding the outcome of the awaited offspring. The recent studies seem to justify some of those doubts.

Australia↗

Invasive procedures in multiple gestations.

PURPOSE OF REVIEW: The incidence of multiple gestations has increased significantly with advances in assisted reproductive techniques resulting in a concomitant increase in invasive procedures in these pregnancies. Commonly performed invasive procedures include amniocentesis, chorionic villus sampling, multifetal pregnancy reduction, and selective termination. Amniocentesis and chorionic villus sampling are also performed in singleton pregnancies, while multifetal pregnancy reduction and selective termination are procedures that are unique to multiple gestations. RECENT FINDINGS: With increased operator experience, pregnancy loss rates after chorionic villus sampling, multifetal pregnancy reduction, and selective termination have decreased to acceptably low levels. Amniocentesis and chorionic villus sampling continue to have similar loss rates in experienced hands. A recent study suggests that amniocentesis in twins may have a higher post-procedural loss rate than in singletons; this may be due to the higher background loss rate of twins. There has been a recent increase in multifetal pregnancy reduction to a singleton with a trend towards improved outcomes over reduction to twins; future studies should focus on whether this confers a definitive advantage. Newer data suggests that selective termination after 20 weeks gestation in experienced hands does not increase loss rates over those procedures performed before 20 weeks. Newer techniques, such as cord coagulation, continue to be developed for selective termination in monochorionic pregnancies, though still with considerable morbidity and mortality. SUMMARY: In summary, invasive procedures in multiple gestations are now commonly performed with. It is our hope that primary prevention of high order multiple pregnancies by optimization of assisted reproductive techniques will decrease the need for these procedures.

Abortion, Eugenic↗

Appraisal of gamete intrafallopian transfer.

OBJECTIVE: To collect results of gamete intrafallopian transfer on a large scale in order to compare treatment indications, results, and factors which influence the success rates; to evaluate whether gamete intrafallopian transfer is well-established and what the real place of this procedure is among other assisted reproduction techniques. DESIGN: Data relating to gamete intrafallopian transfer were collected from World Reports, national registries of different countries and meta-analysis of medical publications during the years 1986-1991. SUBJECT: Official registries reported 47,200 treatment cycles and 18,759 treatment cycles were analysed from ten medical publications. RESULTS: The procedure accounts for 13.5% of all assisted reproduction techniques but its popularity varies significantly among countries. The same indications for gamete intrafallopian transfer are followed by all countries, but great differences exist with regard to the proportional share of each etiology. Also, the share has changed considerably over the years. TREATMENT OUTCOME: 10,667 clinical pregnancies were reported which represent 24% of treatment cycles and 29% of ovum pick-up. The live birth rate was 23.3%; abortion rate, 22%; and ectopic pregnancy rate, 5.5%. The stillbirth rate was 2.3% and the malformation rate was 2.8%, not confined to specific organs or systems. There were 19.5% twins, 4.6% triplets and 0.3% quadruplets or more. The number of transferred oocytes influenced pregnancy rates: 28% for transfer of four oocytes and only 10% following transfer of one oocyte. The cause of infertility might influence the results and the poorest results are obtained for male factor infertility. In most cases correlation of success rates reported by leading units through medical publications closely resembles the overall national registries results. Indications for this treatment were broadened over the years, but its role among other assisted reproduction technologies is not agreed upon, especially for male factor and unexplained infertility. CONCLUSIONS: Gamete intrafallopian transfer carries an overall higher pregnancy rate than in vitro fertilization. Quality control by professional or public associations should be established and more research employed over indications for treatment and results in order to establish when GIFT is the treatment of choice and when other modes of treatment should be preferred.

Australia↗

Reproductive outcomes in women with uterine anomalies.

PURPOSE: Because of diagnostic improvements in the evaluation of uterine anomalies, more patients desirous of pregnancy come to clinicians with identified uterine anomalies. It is desirable for the family physician, internist, and obstetrician/gynecologist to provide accurate information during preconceptional counseling of these patients. This review attempts to provide a concise summary of the current English-speaking literature concerning the reproductive outcome in women with uterine anomalies following both natural conceptions and those pregnancies occurring with assisted reproductive techniques (ART). METHODS: A literature review of reproductive anomalies and pregnancy outcomes was performed using PubMed databases. Obstetrical outcomes were compiled from the medical literature and compared with the known rates of pregnancy outcomes in subjects presumed to have normal uterine anatomy. RESULTS: In general, obstetrical complications, such as preterm delivery and first trimester miscarriage, are higher in women with abnormal uteri. Women with an arcuate uterus have a similar reproductive outcome to women with a normal uterus. The unicornuate uterus has the poorest overall reproductive outcome, and the septate uterus has an increased miscarriage rate. The didelphic uterus, historically thought to have no adverse reproductive outcomes, also has poor obstetrical outcomes. Didelphic, bicornuate, unicornuate, and septate uteri have lower pregnancy rates in ART. CONCLUSIONS: Women with uterine anomalies have poorer reproductive outcomes and lower pregnancy rates with all conceptions whether spontaneous or induced with ART compared with women with normal uteri.

Female↗

Prevalence and outcome of pregnancies in Norwegian and Swedish women with cystic fibrosis.

BACKGROUND: As patients with cystic fibrosis now live longer, more women with cystic fibrosis wish to become mothers. We looked at the prevalence and outcome of pregnancies in women with cystic fibrosis who were alive in Norway and Sweden in the year 2000. METHODS: Women with cystic fibrosis aged 18 years and older attending cystic fibrosis centers in Norway and Sweden were included in the study. Information was obtained from medical records, interviews and questionnaires. RESULTS: One hundred and thirty-two women with cystic fibrosis were included. Sixty-one (46%) had considered or were now considering pregnancy. Forty-six (75%) of these 61 women had already conceived. Eighty pregnancies were reported, including 12 (15%) conceived by assisted reproductive techniques. There were eight (10%) induced abortions, 11 (14%) miscarriages, and one extrauterine pregnancy. The remaining 60 (75%) pregnancies resulted in live born infants. CONCLUSIONS: Today women with cystic fibrosis have a better chance of getting pregnant than previously reported. In this study, 75% of those who wanted to get pregnant had succeeded. Fifteen percent of pregnancies were conceived by artificial reproductive techniques. The possibility of motherhood must be considered in these patients. It is important to plan pregnancies with optimal follow up by a cystic fibrosis team.

Abortion, Induced↗