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PubMed1989

Human oviductal fluid (hOF) proteins. IV. Evidence for hOF proteins binding to human sperm.

In the management of infertile patients, it is well recognized that gamete intrafallopian transfer (GIFT) has a higher success rate than in vitro fertilization and embryo transfer. Oviducts produce unique proteins that may be responsible for the success of GIFT. Unique proteins from human oviductal fluid (hOF) have been purified in the authors' laboratory. One of these proteins of 54 kDa molecular weight, and containing carbohydrate, was obtained in a highly purified state. In this study, human sperm were incubated with: (1) a mixture of hOF-specific proteins, and (2) the highly purified hOF glycoprotein, designated human oviductin I (hOV-I). Using indirect immunofluorescence, the authors studied the ability of hOF proteins to bind to human sperm. The mixture of hOF proteins appeared to bind to the surface of the entire sperm. Conversely, hOV-I binding was restricted to the head region only. Studies are in progress to discern the function of the sperm-binding interaction(s) with hOF proteins.

Fallopian Tubes↗

PubMed1999

The cost of infertility evaluation and therapy: findings of a self-insured university healthcare plan.

OBJECTIVE: To assess the total costs of infertility coverage, determine the proportion of healthcare costs related to infertility, compare infertility costs to those of other diseases, and calculate a per member per month cost of an infertility benefit. DESIGN: Historical prospective analysis. SETTING: A university-based, self-insured, fee-for-service healthcare plan. PATIENT(S): Healthcare policy members from January 1993 through December 1995. INTERVENTION(S): General and infertility-specific healthcare that included diagnostic tests for infertility, induction of ovulation, artificial insemination, donor gametes, in vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, microsurgical epididymal sperm aspiration, embryo cryopreservation, and frozen embryo transfer. MAIN OUTCOME MEASURE(S): Healthcare costs, as calculated from the International Classification of Diseases, Volume 9 codes. RESULT(S): Total healthcare and infertility-specific costs of the university healthcare plan over a 3-year period were $86,445,642 and $680,921, respectively. Therefore, infertility accounted for 0.79% of the total university healthcare costs. The mean total and infertility-specific per member per month healthcare costs were $86.15 and $0.67, respectively. CONCLUSION(S): These data reveal that infertility costs account for only a small fraction of the total healthcare costs and can be attained at a nominal monthly fee.

Adolescent↗

PubMed2002

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

OBJECTIVE: To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. METHODS: This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. RESULTS: Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. CONCLUSION: Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.

Adult↗

PubMed1988

Analysis of 1071 gift procedures--the case for a flexible approach to treatment.

An analysis of the outcome of first gamete intrafallopian transfers for 1071 women indicates that for those aged 40 years or more all the oocytes had to be transferred to obtain a 19.2% pregnancy rate. In this age-group pregnancy rate and multiple pregnancy rate were significantly lower than those for younger women. Success rate, but not multiple pregnancy rate, was significantly higher in the group of women from whom 11 or more oocytes were recovered and transferred after ovulation induction than when only 1-4 oocytes were recovered and transferred. The findings suggest that the number of oocytes transferred should depend on clinical circumstances.

Abortion, Spontaneous↗

PubMed1991

Resources for infertility treatment.

Infertility is common, a serious medical problem in both advanced and underdeveloped countries. At present, medical resources are often used very haphazardly and frequently extravagantly to combat fertility problems. Whilst it seems very unlikely that society will be able to prevent infertility effectively, there is no doubt that the resources available could be better organized for greater benefit. There is evidence of poor co-ordination of services, of inadequate financial planning by health managers, and squandering of limited resources by professionals. Better organization of in vitro fertilization (IVF), with the promotion of larger regional services, would be an effective use of finances. IVF is too often only available to the wealthy and the selection of patients for treatment is frequently arbitrary; many fertility treatments are of unproved value and are wasteful. It is argued, for example, that many patients receiving gamete intrafallopian transfer (GIFT) for so-called 'unexplained infertility' would be better treated by other, less expensive, methods which are often more effective. Many useful treatments, such as tubal surgery, are being disregarded or misused and there is need for better education of specialists who treat infertile patients. Better primary care of infertile patients should include non-medical counselling, and investigation and firm diagnosis before treatment is commenced. The heavy accent on high technology in the treatment of infertility is often misplaced, and we need to strike a careful balance if resources are to be properly allocated.

Adaptation, Psychological↗

PubMed1993

Endometriosis: medical therapy.

The management of women with endometriosis is complex and necessitates individualization of patient care. The most commonly used medical therapies are danazol, GnRH agonists, medroxyprogesterone acetate and gestrinone. Studies to date have shown these drugs to have equal efficacy in terms of reduction in laparoscopic score and relief of symptoms. However, their side-effects make them unsuitable for long-term use. The addition of low dose hormone replacement therapy to GnRH agonist regimens may allow prolonged use but the current cost of these agents is high. Low dose oral contraceptive pills deserve further investigation. The role of medical treatment for women with endometriosis and infertility is controversial. There is no place for hormonal therapy in such women with stage I or II disease. When expectant management fails, gamete intrafallopian transfer offers excellent results. For those with stage III or IV disease, surgery is preferable with adjunctive medical therapy in selected cases. If pregnancy does not ensue, in vitro fertilization and embryo transfer are the next line of management, and results are optimized by prior medical therapy and aspiration of endometriomas. Major advances have been made in the medical management of endometriosis. However, current treatment strategies are ineffective in eliminating the disease in most women. New approaches are required in both basic and clinical research in order to finally eradicate this often devastating disease.

Danazol↗

PubMed1998

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome.

Luteinizing hormone releasing hormone (LHRH) agonists have been used in conjunction with gonadotrophins, and occasionally with pulsatile LHRH, for ovulation induction in women with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS) and also for superovulation for in vitro fertilization (IVF) and gamete intrafallopian transfer in women with PCOS. In IVF, LHRH agonists given by the 'long protocol' before gonadotrophins are commenced have consistently shown higher pregnancy rates and higher live birth rates. Although the optimal time to commence LHRH agonist is not clearly determined, commencement in the early follicular phase possibly with pre-treatment with the combined oral contraceptive pill would avoid the risk of inadvertent administration during early pregnancy. The role of LHRH agonists in ovulation induction is less clear cut, although there may be some advantages in patients with refractory PCOS. The role of LHRH agonists in ovarian hyperstimulation syndrome and recurrent miscarriage is also discussed.

Abortion, Habitual↗

PubMed1996

Management and outcomes of 65 quadruplet pregnancies: sixteen years' experience in France.

OBJECTIVE: Data on the prognosis and management of multifetal pregnancies are of vital importance, particularly when the option of selective termination is considered. The present study details the obstetric management, neonatal outcome, and follow-up data of 65 quadruplet pregnancies in France. METHODS: To conduct the study, a questionnaire was sent to families registered with the National Association Helping Parents of Multiple Births (Association National d'Entraide des Parents de Naissance Multiples, A.N.E.P.N.M.). RESULTS: Of 116 questionnaires sent to families of quadruplets born between 1972 and 1988, 65 were received. Of these pregnancies, 58 were obtained with ovulation induction agents, 2 with IVF (in vitro fertilization) and GIFT (gamete intrafallopian transfer) and 5 were spontaneous. Diagnosis was made prior to 13 weeks gestation in 87.2% of cases. Most mothers were hospitalized prior to delivery--mean duration of 47 days. The mean gestational age at delivery was 31.2 +/- 3 weeks with a prematurity rate of 97%. Cesarean sections were performed in 51 cases and vaginal deliveries in 14. Neonatal and perinatal mortality rates were 68 and 104 per 1000, respectively. Birthweights of quadruplets ranged from 760 to 2455 g with a mean of 1615 g. CONCLUSION: Management of quadruplet pregnancies in France consists of early diagnosis, echographical and clinical monitoring, early reduction of maternal activity and cesarean deliveries. Our management of such pregnancies is of high quality as reflected by our obstetrical results. Lack of adequate management, as perceived by families of quadruplets, exists at two levels; a psychological (lack of psychological support) and a financial (lack of specific help).

Birth Weight↗

PubMed1989

Detection and treatment of antispermatozoal antibodies in men.

Autoimmunity to spermatozoa results in the production of antisperm antibodies that usually reduce the fertility of human males. Many laboratory tests have been devised to detect antisperm antibodies, but the results of such tests do not always correlate well with each other, particularly when the tests are conducted with patients' own spermatozoa rather than donor sperm. Experience over the past 12 years at Chelsea Hospital for Women and St Bartholomew's Hospital in London has led to at Chelsea Hospital for Women and St Bartholomew's Hospital in London has led to the development of an effective method for testing and treating subfertile males. This involves using the mixed antiglobulin reaction test and the post-coital test as initial screening tests, followed by serum and seminal plasma agglutination tests (both gelatin and tray) and the sperm-cervical mucus contact tests. Suitable patients are then put on one of three steroid regimens--long-term low-dose prednisolone, intermittent high-dose methylprednisolone, or intermediate graduated-dose prednisolone. Such treatment is useful not only in cases of spontaneous autoimmunity, but also in cases involving genital infection, testicular obstruction, and in vitro fertilization or gamete intrafallopian transfer.

Autoantibodies↗

PubMed1999

The management of unexplained infertility.

UNLABELLED: Unexplained infertility is a diagnosis made by exclusion after all of the standard investigations have revealed no abnormality (1). The range of the prevalence is from 6 to 60 percent (23), depending on the diagnostic criteria. This article reviews the literature in the management of unexplained infertility; published data suggest no benefit of danazol or bromocriptine. The empirical use of clomiphene citrate suggests that ovarian stimulation using clomiphene citrate can double the spontaneous pregnancy rate (52, 58, 59). Induction of ovulation with human menopausal gonadotrophin (hMG) yields an overall pregnancy rate between 2 and 26 percent per cycle (68, 74). These results seem to be lower than those reported for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) procedures in similar patients (25-30 percent (92, 95)). Based on the literature, a rational treatment plan for treating infertility in couples with unexplained infertility includes up to four cycles of clomiphene citrate with or without intrauterine insemination (IUI). Superovulation with hMG and IUI or stimulated intrauterine insemination (SIUI) is the next step for three-cycle treatments and if unsuccessful, one of the variants of assisted reproductive techniques (ART) should be considered. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will understand the appropriate tests and work up for unexplained infertility, the various treatment options for the unexplained infertility couple including which drugs are effective and not effective, and to be able to outline an appropriate treatment plan for such patients.

Diagnostic Techniques, Obstetrical and Gynecologic↗

PubMed1990

An ethical issue for reproductive technologies.

The establishment of "new birth technologies" (such as ovulation induction, in vitro fertilization and gamete intrafallopian transfer) has raised many ethical issues. One such issue is "selective fetal reduction", a process advocated in the management of excessive multiple pregnancy. The ethics of "selective fetal reduction" involve consideration of not only the efficacy of the process and the destruction of fetuses per se, but more specifically consideration of the moral dilemma of destroying some fetuses for the probable benefit of the remainder. The latter I consider here. Following from this ethical analysis it is suggested that the law regarding abortion should permit selective reduction in high multiple pregnancies, that is pregnancies of 4 or above. I contend that the law should prohibit deliberate exposure (in an infertility programme) to significant risk of high multiple pregnancy, when there is full intention to reduce any subsequent pregnancy of high multiple size.

Abortion, Induced↗

PubMed1995

Autoimmune premature ovarian failure.

Premature ovarian failure (POF) may be caused by a variety of factors that result in the depletion of responsive ovarian follicles. There is a increasing body of evidence that suggests an autoimmune etiology in some POF patients. Data in support of an autoimmune etiology include: (1) lymphocytic and plasma cell infiltration of the ovary and alteration of T cell subsets; (2) circulating autoantibodies to ovarian antigens; (3) association with other "autoimmune" disorders; (4) recovery of ovarian function after regression of autoimmune status. The mechanism for ovarian autoimmunity is unknown. Genetic or environmental factor might be involved in the stimuli inducing immune response. The possibility that major histocompatibility complex antigen and cytokines are implicated in human autoimmune POF has been proposed. The relative contribution of cell-mediated immunity and antibody-mediated immunity remains obscure in animal models and in POF patients. Currently, in vitro fertilization and/or gamete intrafallopian transfer with donated oocytes are the best therapeutic options to achieve pregnancy although ovulation induction and immunosuppressive treatment might be used in approved experimental protocols. A newly developed double bridged enzyme linked immunosorbent assay (ELISA) might be useful in screening POF patients to identify those for whom temporary treatments may improve fertility.

Antibodies↗

PubMed1989

Abnormal cornual ostia and infertility.

Hysteroscopy performed on 126 infertile patients and on 73 fertile patients revealed a significant association between abnormal uterine cornual ostia and infertility (p less than 0.002). Ostial abnormalities included absence of cupping with uterine cavity distension, diminution of ostial diameter and complete ostial occlusion. High intrauterine pressures from dye perturbation can overcome the occluded ostial state giving a false impression of adequate tubal patency. These findings may explain some cases of apparently unexplained infertility and may bear on the success rates of procedures such as artificial insemination and gamete intrafallopian transfer.

Female↗

PubMed1994

Folliculogenesis--the stimulated way.

The initial techniques of stimulating follicular development in the anovulatory woman involved the use of human pituitary gonadotrophin (hPG) and thus replaced the function of the pituitary gland. Despite extreme care with administration of hPG and extensive monitoring to assess the ovarian response, ovarian hyperstimulation and multiple pregnancy were common. Less expensive and easier methods of treatment soon followed with oral clomiphene citrate (early 1960s), oral bromocriptine (early 1970s) and pulsatile gonadotrophin-releasing hormone (late 1970s) being used. Currently all of these methods, alone or in combination, are employed and successful ovulation induction (except in women with elevated FSH levels) can now virtually be guaranteed. Controlled ovarian hyperstimulation, just the outcome one was attempting to avoid in the treatment of anovulatory women, has become the treatment of choice for women having in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). The extra oocytes produced by this treatment results in more embryos being available for transfer and/or freezing and improves the overall pregnancy rate. The concurrent use of gonadotrophin-releasing hormone agonists (GnRH-a) has resulted in more mature oocytes being developed, less cancelled cycles for a spontaneous midcycle LH surge, and allowed even more embryos to be produced thereby increasing the pregnancy rate further to the current expected 20% per cycle commenced. As techniques are further modified, adverse effects of elevated LH levels on pregnancy and take home baby rates should be able to be overcome, and oocyte freezing and long-term storage should become a possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromocriptine↗

PubMed2001

Follicular flushing at oocyte retrieval: a reappraisal.

A survey of Australian assisted reproduction technique (ART) units revealed many (> 50%) use flushing of the follicle in addition to direct aspiration of the fluid during oocyte retrieval. The rationale is that flushing offers an advantage to the patient, with a larger number of oocytes being collected and thus a higher potential for pregnancy Following a complication in a patient, the medical staff determined that flushing might have been implicated. While this was later shown to be unfounded, the unit changed the method of oocyte collection, thus providing an opportunity historically to evaluate the differences between aspiration of follicular fluid alone or with additional flushing of each follicle. Thus the aim of this analysis was to test the hypothesis that aspiration alone does not effect the outcomes of ART with respect to oocyte numbers collected, their quality and subsequent fertilisation, or ultimate pregnancy rate in a large patient group (n = 2378). During the review period (1991-1993) the manufacturer of the aspiration needles; the pump and pressure used for aspiration; the staff involved in all procedures; and the premises, equipment and media used for oocyte collection and culture remained constant. Similarly the two patient groups did not differ in their demographics and physical characteristics. There was no difference (p > 0.5) in the number of oocytes collected, the number of embryos created or the pregnancy rate for that treatment cycle. There was also no significant difference between the two groups in fertilisation rates, irrespective of the type of treatment being used in vitro fertilisation (IVF), gamete intrafallopian transfer (GIFT) or intracytoplasmic sperm injection (ICSI)). The data presented in this paper are not prospective. They use historical comparison and are confounded by minor changes in ovarian stimulation protocols, but the conclusions are still valid. These data suggest there is no difference in the outcome of ART (from oocyte collection through to pregnancy rate) whether or not aspiration of follicles is accompanied by flushing. First principles of surgery advocate the shortest possible operating time, the simplest procedure and minimum amount of tissue handling as maxims for reducing complication. Therefore, as a routine, flushing would seem superfluous in ART.

Female↗

PubMedDate not supplied

Immunological role for seminal plasma in insemination and pregnancy.

Insemination confronts the female with paternally derived alloantigens and represents an immunological challenge preceding fertilization and implantation. Current evidence suggests a role for seminal plasma in regulating maternal immunity for insemination and pregnancy. In vitro seminal plasma has been shown to suppress T- and B-cell proliferation, neutrophil and macrophage phagocytic activity, as well as killer cell activity. Seminal plasma interacts with complement components C1 and C3 and contains factors that specifically bind the Fc region of IgG. These in vitro findings suggest possible seminal plasma-suppressive effects on female alloimmune responses after insemination. Seminal plasma also contains allotypic TLX antigens that could prime mothers prior to fertilization. Such priming effects for pregnancy acceptance are supported by improved implantation rates in controlled clinical trials using timed vaginal exposure to semen during in vitro fertilization or gamete intrafallopian transfer treatment cycles.

Female↗

PubMed2004

Modalities for treatment of antisperm antibody mediated infertility: novel perspectives.

Immunoinfertility because of antisperm antibodies (ASA) is an important cause of infertility in humans. The incidence of ASA in infertile couples is 9-36% depending on the reporting center. Early claims regarding the incidence and involvement of ASA in involuntary infertility were probably overemphasized, which has resulted in subsequent confusion, doubt, and underestimation of their clinical significance. No immunoglobulin that binds to sperm should be called an antisperm antibody in a strict sense unless it is directed against a sperm antigen that plays a role in fertilization and fertility. ASA directed against the fertilization-related antigens are more relevant to infertility than the immunoglobulins that bind to sperm associated antigens. Several methods have been reported for treatment of immunoinfertility. These include: immunosuppressive therapies using corticosteroids or cyclosporine; assisted reproductive technologies such as intrauterine insemination, gamete intrafallopian transfer, in vitro fertilization, and intracytoplasmic sperm injection; laboratory techniques such as sperm washing, immunomagnetic sperm separation, proteolytic enzyme treatment, and use of immunobeads. Most of the available techniques have side effects, are invasive and expensive, have low efficacy, or provide conflicting results. Recent findings using defined sperm antigens that have a role in fertilization/fertility have provided animal models and innovative novel perspectives for studying the mechanism of immunoinfertility and possible modalities for treatment. The better understanding of local immunity and latest advances in hybridoma and recombinant technologies, proteomics and genomics leading to characterization of sperm antigens relevant to fertility will help to clarify the controversy and to establish the significance of ASA in infertility.

Adrenal Cortex Hormones↗

PubMed1991

Cocultures in human assisted reproduction. Support of embryos in vitro and their specificity.

Assisted reproductive techniques (ART) have contributed tremendously to alleviating infertility in childless couples. However, the "take-home baby" rate for in vitro fertilization (IVF) has been much below the rate for normal fertile couples and for the other tubal procedures such as gamete intrafallopian transfer (GIFT) and tubal embryo transfer (TET). It was therefore speculated that the tubal environment might be playing an important role towards the viability of the embryo and that, in IVF, 4-6 cell stage embryos that were usually replaced directly into the uterus might not be receiving the beneficial effects of the tubal environment. Pronuclear stage human and mouse embryos were thus cocultured with reproductive and other somatic cell types to evaluate the quality of the various cleaving stages and the percentage yield of blastocysts. Human ampullary cell cultures were established in 6 to 7 days and kept alive through one menstrual cycle. Cleavage to the compacted and cavitating stages was achieved in 78% and 69%, respectively, of human embryos cocultured in 24-48 hour human ampullary subcultures as compared to 50% and 33%, respectively, for embryos grown in culture medium alone. The percentages of expanded blastocysts and hatching stages in such cocultures were not significantly different from those of controls. However, human ampullary and cumulus and mouse ampullary and muscle fibroblast cultures supported cleavage and development of mouse embryos up to the hatching stages as well as or better than controls. It thus appears that there is no absolute specificity for a reproductive tract source of cocultured cells and that the beneficial effects of ampullary and cumulus cells are not species-specific. The coculture system also appears to overcome the embryonic blocks of the human and mouse, which may be mediated via growth factors that activate the embryonic genome.

Animals↗