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Human pregnancy after transfer of intact frozen-thawed embryos.

Since the birth of the first baby as a result of in vitro fertilisation (IVF) in 1978, many clinics around the world have achieved pregnancies and births for their patients by using IVF and gamete intrafallopian transfer procedures. With the storage of excess embryos, multiple laparoscopies can be avoided; this has favoured the development of better cryopreservation techniques. In our clinic 8-cell human embryos are frozen in a 1.5M dimethyl sulphoxide solution as cryoprotectant using the slow freeze-thaw method. Sixteen thawed embryos were replaced in 8 patients, resulting in 1 pregnancy. Of the thawed embryos 51.6% survived the freezing process in that they had 50% or more of the original number of blastomeres and also the zona pellucida intact.

Cryopreservation↗

Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer.

PURPOSE: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. METHODS: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/ mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. RESULTS: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. CONCLUSIONS: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.

Adult↗

In vitro and xenogenous capacitation-like changes of fresh, cooled, and cryopreserved stallion sperm as assessed by a chlortetracycline stain.

Like the human female, the mare experiences reproductive tract pathology that may sometimes be circumvented by the use of assisted reproductive technologies (ARTs). One such technology, gamete intrafallopian transfer (GIFT), may be used in mares that exhibit ovulatory, oviductal, or uterine abnormalities that limit the use of common ARTs, such as embryo transfer. Homologous GIFT has been successfully performed in the horse; however, the logistics, costs, and associated risks of surgically transferring gametes to the oviducts of a recipient mare are considerably high. Use of a less costly species in a heterologous or xenogenous procedure would therefore be beneficial. This study represents the preliminary investigation into the use of sheep as recipients for xenogenous GIFT procedures using equine gametes. We investigated the capacitation response of fresh, cooled, or frozen stallion sperm after 1) in vivo incubation in the reproductive tract of estrous and anestrous ewes as well as 2) in vitro incubation in a modified Krebs/ Ringer extender at 37 degreesC with and without the addition of heparin at 10 IU/mL for up to 8 hours. A chlortetracycline (CTC) fluorescent stain was used to assess the capacitation response of sperm. Findings indicated that oviductal fluid samples recovered from estrous ewes had significantly higher numbers of sperm exhibiting capacitation-like staining patterns when compared to samples recovered from anestrous ewes (P < .05). Fresh semen yielded higher capacitation-like staining patterns after in vivo incubation than did frozen-thawed or cooled samples. A transition from majority CTC unreacted sperm to majority CTC non-acrosome intact sperm was demonstrated for both in vivo and in vitro studies. In vitro incubation of stallion sperm with heparin did not result in an increased capacitation-like staining response over time when compared with nonheparinized samples. Results from this study suggest that xenogenous capacitation of stallion sperm may occur in the estrous ewe.

Anestrus↗

Surgical techniques of oocyte collection and embryo transfer.

In the decade since the birth of the first child conceived as a result of in vitro fertilization and embryo transfer much has been achieved in the field of assisted conception. Although in vitro fertilization (IVF) was successful first for the treatment of tubal disease, the indications for its use have now widened to include unexplained infertility, oligozoospermia, endometriosis and infertility due to immunological disorders. Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) are now used commonly for the treatment of couples where the woman has patent fallopian tubes. The huge increase in the demand for therapy using these techniques of assisted conception places considerable strain on the finances available for health care, and has led some to question the wisdom of such use of limited resources. To reduce the cost of treatment, and because repeated IVF-ET attempts may be necessary before achieving pregnancy, the initial laparoscopic approach for oocyte recovery has been largely replaced by ultrasound-guided techniques. Non-surgical embryo transfer techniques have changed little since originally described. However, where the tubes are patent, one-cell zygotes or cleavage stage embryos may be transferred into the fallopian tube (ZIFT and tubal embryo stage transfer respectively). On the other hand if the tubes are blocked, surgical embryo transfer (SET) may be performed. Most recently, some success has been achieved following the transfer of embryos into the fallopian tube by the technique of retrograde fallopian tube catheterisation.

Biopsy, Needle↗

[Developmental trends in reproduction medicine].

In the last few years reproductive medicine has developed into a medical research field of its own. It deals with the theoretical and practical problems of human reproduction and is characterized by close cooperation between medical and scientific specialists both clinically and in research. Far-reaching social effects arise from the application of hitherto unknown research and treatment methods. The results of research in reproductive medicine led, due to the development of effective contraceptives, to a reduced connection between sexual intercourse and reproduction, and have made possible reproduction even without sexual intercourse, by means of artificial insemination and in-vitro fertilization. These latest and most exciting developments in reproductive medicine are based on and justified by the right of every couple to a child of their own. In-vitro fertilization and related treatments, eg. gamete intrafallopian transfer, are expected to dominate the treatment of the sterile couple in future. The social effects of the new techniques in reproductive medicine nessecitate the development of ethical standpoints, in which human welfare must predominate. In the GDR, in accordance with the recommendations of the "Ethics in medicine" working group, in-vitro fertilization using gametes of the same couple is ethically accepted, as is also oocyte and embryo donation, provided they aim to fulfil a couple's wish for a child. Surrogate mothers are rejected, however. The combination of in-vitro fertilization and genetic engineering could potentially be used in the treatment of certain types of hereditary disease, but there is also the possibility of misuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Outcome and complications of assisted reproduction.

This review discusses studies documenting an increase in birth rate associated with in vitro fertilization and gamete intrafallopian transfer. The results of zygote intrafallopian transfer are also encouraging. The rates of chromosomal and congenital abnormalities in assisted reproduction are similar to the rates at which these problems occur in normal pregnancies. Multiple pregnancy is the main determinant of outcome. Singleton pregnancies have higher rates of pregnancy complications. Factors affecting outcome of assisted reproduction include age of the mother, level of basal follicle-stimulating hormone, the number of embryos or gametes transferred, response to ovarian stimulation, and the quality of gametes and eventually of the embryo. Complications of these procedures relate to the technique used. Recent reports have highlighted the effects of multiple gestation in terms of perinatal morbidity, the effect on the family, and the demand for neonatal resources, as well as ethical issues surrounding selective reduction. The use of gonadotropin-releasing hormone agonist has led to an increase in the incidence of severe ovarian hyperstimulation. Other reports document the incidence of ectopic pregnancy in in vitro fertilization with embryo transfer.

Birth Rate↗

Enhancement of human sperm motility and velocity in vitro: effects of calcium and creatine phosphate.

Because of their roles in motility regulation and energy transport, calcium and creatine phosphate were examined for their effects on sperm motility and velocity in specimens of normal donors. Semen or migrated sperm fractions were incubated with of 1 mmol of calcium, 5 mmol magnesium, and 10 mmol of creatine phosphate (n = 28) or in the presence of 4 mumol of Verapamil, calcium, and creatine phosphate (n = 10). The samples were subjected to multiple exposure photography (four picture frames of two different drops) at 0, 1, 4, or 5 and at 10 hours and sperm motility and velocity were analyzed. In both calcium and calcium-creatine phosphate conditions, sperm motility and velocity were significantly increased, compared with control values (P = between less than 0.001 and 0.05). Sperm motility declined following Verapamil exposure, but the motility values remained at the level of the control in the presence of additional calcium or creatine phosphate. The effects of calcium and creatine phosphate take place rapidly; within 1 minute all improvements in sperm velocity and motility are fully achieved. There is no loading effect of calcium, and when the sperm is transferred into media without the additional calcium, the velocity decreased to that of the initial control value. Magnesium alone had no effect on motility or velocity. These experiments indicate that calcium or creatine phosphate can support sperm motility and velocity at a significantly increased level. Thus the addition of calcium or creatine phosphate to the insemination media may enhance the fertilizing capacity of sperm during in vitro fertilization or gamete intrafallopian transfer procedures.

Calcium↗

Infertility update: use of assisted reproductive technology.

OBJECTIVE: To describe assisted reproductive technology (ART) and use of medications during these procedures. DATA SOURCES: Recent clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: ARTs are procedures used in treatment of infertility that involve removal of oocytes and their manipulation outside the woman's uterus. The simplest form of ART, in vitro fertilization, involves aspirating eggs from the ovaries, fertilizing them outside the body, and transferring the embryos into the uterus at the four- to eight-cell stage. Experimental regimens for in vitro fertilization include use of various medications (gonadotropin-releasing hormone agonists, human menotropins, follicle-stimulating hormone, growth hormone) at varying points in the menstrual cycle and after introduction of the embryo into the uterus. Human chorionic gonadotropin has been used to increase implantation of embryos during the woman's luteal phase. Gamete intrafallopian transfer (GIFT) involves transfer of oocytes and sperm into the fallopian tubes, where fertilization takes place. This technique has the advantage of causing the zygote to enter the uterus at the time it would during natural conception. Zygote intrafallopian transfer is similar to GIFT, except that fertilization occurs in vitro, with embryos placed in the fallopian tubes at the two-cell stage. Various micromanipulation techniques and innovative sperm aspiration procedures are currently under development. CONCLUSION: Many advancements have been made in ART, and pharmacists who understand these procedures can serve patients by providing medication information in an empathetic and supportive manner.

Female↗

[Transvaginal, ultrasound-controlled follicle puncture].

Between December 1986 and November 1987, 588 transvaginal sonographically-guided oocyte retrievals, using a vaginal transducer, were performed for in vitro fertilization at the University of Bonn. All follicles were accessible. No complication occurred except one case of pelviperitonitis in a patient with preoperatively diagnosed sactosalpinx. Because this technique is safe, non-invasive, and performable without general anaesthesia, we also retrieved eggs in patients despite poor hormonal values and endogenous LH-surge. In all, clinical pregnancies were diagnosed in 85 patients. Pregnancy rates per embryo transfer, oocyte retrieval and stimulated cycle, respectively were 19.0%, 14.5% and 12.0%. The advantages of the transvaginal technique, using a vaginal transducer compared with the laparoscopically-guided as well as with other sonographically-guided techniques of oocyte retrieval, are obvious (possibly without general anaesthesia, in general all follicles are accessible, very low complication rates, low discomfort to patient, and less amount of time and staff). Therefore, this technique seems to be the method of first choice. A laparoscopically-guided oocyte retrieval is only indicated, when a laparoscopic screening of pelvic organs or a gamete intrafallopian transfer are to be performed simultaneously.

Embryo Transfer↗

In vitro fertilization-embryo transfer (IVF-ET) in the United States: 1990 results from the IVF-ET Registry. Medical Research International. Society for Assisted Reproductive Technology (SART), The American Fertility Society.

OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive technology (ART) initiated in the United States in 1990. DESIGN: The registry follows a prospective study format. PARTICIPANTS: One hundred eighty clinics submitted data on their ART treatments to the In Vitro Fertilization (IVF) Registry. MAIN OUTCOME MEASURES: The outcomes measured included clinical pregnancy, ectopic pregnancy, abortion, stillbirth, delivery, chromosomal abnormalities, and congenital defects. RESULTS: During 1990, the clinics reported performing 25,744 ovarian stimulation cycles. From all ART treatments there were 5,150 clinical pregnancies and 3,951 live deliveries. The overall live delivery rates were 14% for IVF (based on 16,405 retrievals), 22% for gamete intrafallopian transfer (based on 3,750 retrievals), and 16% for zygote intrafallopian transfer and related practices (based on 1,370 retrievals). The delivery rates for frozen embryo transfer cycles and IVF with donor egg cycles were 9% and 22%, respectively. CONCLUSIONS: The 1990 results indicate an increase in the use of gonadotropin-releasing hormone analogs and an increase in the number of embryos being transferred per cycle, along with no important changes in clinical pregnancy and delivery rates. In addition, there was an increase in both numbers of frozen embryo transfers and IVF cycles with donor oocytes.

Abortion, Spontaneous↗

Comparison of sperm binding potential of uninseminated, inseminated-unfertilized, and fertilized-noncleaved human oocytes under hemizona assay conditions.

In this study, human oocytes obtained after ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) were utilized to evaluate sperm/zona pellucida binding potential. Three groups of oocytes were evaluated: 1) uninseminated; 2) inseminated-unfertilized; and 3) fertilized-uncleaved. All oocytes had undergone germinal vesicle breakdown at the time of retrieval and were salt-stored (pH 7.2) for not more than 30 days. Sperm binding was recorded under hemizona assay (HZA) conditions using spermatozoa from eight fertile men (HZA control) and from 1) four teratozoospermic (HZA test) and 2) four normozoospermic (HZA test) infertile men. First, the mean numbers (+/- SD) of sperm tightly bound for fertile controls and teratospermic men to hemizonae from uninseminated oocytes were 69.7 +/- 16 and 14.5 +/- 7, respectively (P = 0.02). Likewise, hemizonae from uninseminated oocytes bound 102.0 +/- 19 and 114.0 +/- 28, respectively, for fertile controls and normospermic men (P = 0.5). Second, hemizonae obtained from inseminated-unfertilized IVF oocytes bound 44.2 +/- 12 and 19.7 +/- 6 for fertile controls and teratospermic men, respectively (P = 0.02). This category of oocytes bound 100.5 +/- 7 and 108.5 +/- 11 sperm, respectively, for fertile controls and normospermic semen (P = 0.3). Third, HZA results of fertilized but uncleaved oocytes showed a mean number of tightly bound sperm of 6.0 +/- 4 compared with 65.0 +/- 1 in control, uninseminated oocytes using fertile sperm. These results demonstrate that uninseminated and inseminated-unfertilized human oocytes, salt-stored under controlled pH conditions, give reliable information regarding sperm binding potential under HZA conditions.

Female↗

The effect of clomiphene citrate on human preovulatory oocyte maturation in vivo.

Sixty-four infertile women underwent diagnostic laparoscopy in the periovulatory period at time-bracketed intervals following their endogenous luteinizing hormone (LH) surge. Forty-eight of these women were studied during natural cycles and 16 had mild oligoovulation and were administered clomiphene citrate (CC) to regulate their cycles. No patient received human chorionic gonadotropin. No patient was undergoing either in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). Follicle puncture was performed and the oocytes were observed immediately for stage of maturation. Oocytes obtained from follicles exposed to CC were found to require an increased interval of time to reach metaphase I compared to oocytes obtained from natural cycles (27.75 +/- 2.2 vs 22.5 hr; mean +/- SE). Furthermore, the interval of time required for metaphase I oocytes to achieve metaphase II was statistically significantly shortened for CC cycles (2.4 hr for CC vs 10 hr for natural cycles. Nevertheless, there was no difference between natural and CC cycles in the time interval between LH surge onset and ovulation. These in vivo findings suggest a direct effect of CC on human oocyte maturation and may help explain the well-established discrepancy between the relatively high ovulation rate and the relatively low conception rate in clomiphene-induced cycles.

Clomiphene↗

The occurrence of ectopic pregnancy with and without clomiphene citrate use in assisted and nonassisted reproductive technology.

An eleven-year review of treatment records of patients who became pregnant as a result of infertility treatment (n = 3692) was conducted. All records were examined to determine whether clomiphene citrate (CC) was used in the cycle of conception and whether or not an ectopic pregnancy occurred. Data were additionally analyzed for the incidence of ectopic pregnancy with and without assisted reproductive technology (ART). The incidence of ectopic pregnancy was similar between CC (3.4%) and non-CC (3.4%) treatment groups receiving non-ART treatment. For non-ART treatments, tubal disease and severe endometriosis resulted in an increase in ectopic pregnancies independent of CC use. The incidence of ectopic pregnancy in patients receiving CC + human menopausal gonadotropin (hMG) for in vitro fertilization (5.4%) and gamete intrafallopian transfer (3.1%) was similar compared to ART treatments with hMG alone. The incidence of ectopic pregnancy was more closely associated with infertility diagnosis rather than CC use.

Adult↗

Follicle stimulating hormone levels on cycle day 3 predict ovulation stimulation response.

AIM: To determine the value of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on cycle day 3 in predicting the ovulation stimulation response in patients receiving exogenous gonadotropins for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT). METHODS: One hundred eleven consecutive females with infertility due to various etiologies were investigated. Cycle day 3 serum levels of FSH, LH, and E2 were determined prior to ovulation induction with a combination of clomiphene citrate and human gonadotropins. Follicular growth was monitored ultrasonically, and when appropriate, oocytes were recruited, counted, graded, and then used, as prearranged, for either IVF or GIFT. Basal hormone levels were compared to the peak E2 concentration, the number of follicles aspirated, and the number of preovulatory oocytes recovered following drug therapy. Details of resulting pregnancies were also recorded. RESULTS: Patients with low basal FSH levels (< 11.5 mIu/ml) yielded a higher mean number of preovulatory oocytes than those with high values (> 11.5 mIu/ml), i.e., 6.7 oocytes per cycle vs 2.5 oocytes (P < 0.001). In the low group 97% of cycles yielded more than three fertilizable oocytes compared to 42% in the high group (P < 0.5). There were 16 term pregnancies (16%) in the low group and 1 (8.3%) in the high group. Basal LH and E2 levels did not improve on the ability to distinguish between different populations of infertile females who responded differently to ovulation induction. CONCLUSION: Cycle day 3 FSH levels are predictive of the ovulation response and probability of pregnancy in stimulated cycles and can be of value in patient selection and counseling in IVF and GIFT programs.

Abortion, Spontaneous↗

Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000.

OBJECTIVE: To describe patterns of preterm birth and low birth weight (LBW) for infants born after assisted reproductive technology (ART) and determine whether these were associated with maternal or treatment characteristics. DESIGN: Retrospective cohort study of national population data of infants conceived through ART. SETTING: Australian birth records from 1996 to 2000. PATIENT(S): Eighteen thousand, four hundred twenty-nine liveborn and stillborn infants conceived through ART. INTERVENTION(S): In vitro fertilization, intracytoplasmic sperm injection, and gamete intrafallopian transfer. MAIN OUTCOME MEASURE(S): Preterm birth and LBW. RESULT(S): Preterm birth and LBW were more common among singletons and twins conceived with IVF and born to nulliparous mothers. Preterm birth and LBW were, respectively, 1.3 times and 1.5 times more likely to occur among singletons conceived by transfer of fresh embryos, compared with transfer of frozen embryos. Preterm birth and LBW was more common among couples who had female-factor infertility compared with male-factor infertility. CONCLUSION(S): The transfer of fresh embryos and female-factor infertility were independently associated with preterm birth and LBW for both singletons and twins after ART.

Adult↗

The perioperative nurse's role in assisted-fertility procedures.

Infertility is the inability to achieve pregnancy within a stipulated period of time (ie, one year) or the repeated failure to carry a pregnancy to term. Advances in assistive reproductive technology have enabled many couples to overcome infertility, but health care providers need to remember that these couples require much support. This article addresses the perioperative nurse's responsibilities during assisted-fertility procedures that are performed in the OR (eg, transvaginal oocyte retrieval, gamete intrafallopian transfer, zygote intrafallopian transfer.

Female↗

Antisperm antibodies in women undergoing intrauterine insemination.

Intrauterine insemination is widely used for the treatment of infertility as a result of cervical or male factors or empirically before in vitro fertilization or gamete intrafallopian transfer. This study was designed to confirm or refute the theoretical concern that intrauterine insemination may induce antisperm antibodies in such women. Serum and cervical mucus were obtained at the first, fourth, and sixth intrauterine inseminations. The serum was screened by the Immunobead test for IgG and IgA. If screening results were positive (greater than 10% binding), antisperm antibodies were titered by the microimmobilization and microagglutination tests. The Immunobead test was performed on the cervical mucus after liquefication with bromelin. Ninety-three patients were followed up prospectively. Of these, 40 completed six intrauterine insemination cycles and the remaining 53 completed four cycles. Low transient antisperm antibody levels were detected in 10.8% of the patients and would not be expected to affect the prognosis for fertility. It is concluded that intrauterine insemination does not induce significant antisperm antibody production in women.

Antibodies↗

Genetic offspring in patients with vaginal agenesis: specific medical and legal issues.

OBJECTIVE: There are new options for genetic offspring in patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome). The reported world experience to date with genetic offspring of patients with vaginal agenesis consists of five pregnancies (including two reported here and two frozen embryos). The specifics of these cases are presented for discussion. STUDY DESIGN: We present a retrospective description of two women with vaginal agenesis and their matched gestational carriers with positive outcome of two live births. Care was delivered in a private in vitro fertilization and gamete intrafallopian transfer program. RESULTS: In vitro fertilization of oocytes gathered from the genetic mother with vaginal agenesis and sperm from the genetic father were transferred to a gestational carrier. Two live births and one blighted ovum pregnancy resulted. CONCLUSION: Until recently, treatment for patients with vaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) has centered on the creation of a functional vagina. The technology of in vitro fertilization and embryo transfer, allowing for collection of oocytes from the genetic mother, fertilization by the genetic father, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic children. The specific medical and legal issues involved in facilitating genetic offspring in these instances must be considered; these include the initial matching of the genetic parents with the gestational carrier, cycle synchronization for in vitro fertilization and embryo transfer, anatomic difficulties of oocyte retrieval, birth certificate documentation, and the current legal status of a gestational carrier.

Adult↗