The oviduct: a neglected organ due for re-assessment in IVF.

The oviduct has long been considered a 'pipeline', a tube allowing transit of spermatozoa and embryos; this perspective has been reinforced by the success of human IVF. Evidence accumulated over several decades, however, indicates that embryos can modulate the metabolism of tubal cells in their environment. Human IVF culture media is based on formulations that pass mouse embryo assays as quality control: the requirements of mouse embryos differ from those of human embryos, and therefore conditions for human IVF are far removed from the natural environment of the oviduct. The preimplantation environment, both in vitro and in vivo, is known to affect the health of offspring through mechanisms that influence imprinting. Recent studies also show that male accessory glands act in synergy with the oviduct in providing an optimal environment, and this represents a further perspective on the oviduct's contribution to harmonious embryo development and subsequent long-term health. The metabolism of the human embryo is far from being understood, and a 'return' to in-vivo conditions for preimplantation development is worthy of consideration. Although results obtained in rodents must be interpreted with caution, lessons learned from animal embryo culture must not be neglected.

Endotoxic shock after gamete intrafallopian transfer.

OBJECTIVE: To report an extremely rare case of endotoxic shock due to Enterobacter cloacae that occurred after laparoscopy for gamete intrafallopian transfer (GIFT) in a nulligravid woman. DESIGN: Private fertility center in Cape Town, South Africa. SETTING: Case report. PATIENT(S): A 34-year-old woman with primary infertility. INTERVENTION(S): Routine preparation for GIFT procedure, sonar aspiration to obtain oocytes, followed by GIFT. Endotoxic shock developed within hours after the procedure, followed by admission to the intensive care unit, intravenous antibiotic therapy, mechanical ventilation, and abdominal hysterectomy. MAIN OUTCOME MEASURE(S): Preventing patient mortality and morbidity. RESULT(S): Discharge from the intensive care unit occurred on day 11 after GIFT, which was day 8 after surgery. A MEDLINE search (1980 to 2003) found no previous literature on endotoxic shock associated with assisted reproduction. CONCLUSION(S): Gram-negative infection with subsequent endotoxic shock after assisted reproductive techniques is extremely rare. As this case report shows, early diagnosis and active management of these cases are mandatory to prevent serious complications and mortality.

Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis.

OBJECTIVE: To perform a systematic review of the literature to determine whether singleton pregnancies resulting from IVF-ET/GIFT are at higher risk for preterm birth (<37 weeks). DESIGN: Literature search and systematic review. SETTING: Medical school. INTERVENTION(S): A MEDLINE search (1965-2000) was performed using the terms "premature labor," "infertility," "pregnancy complications," "gonadotropins," "pregnancy outcome," "preterm delivery," and "in vitro fertilization." Criteria for inclusion were English language, original research article, study patients conceived using IVF-ET (with or without intracytoplasmic sperm injection) or GIFT, pregnancy outcome reported compared with a control group (e.g., naturally conceived singletons at their hospital or a national reference), and prematurity clearly defined. Incomplete articles (e.g., abstracts), reports of other studies, and studies that failed to separate multiple from singleton gestations were excluded. MAIN OUTCOME MEASURE(S): Summary of relative risks of preterm birth. RESULT(S): Twenty-seven articles met all inclusion/exclusion criteria and were analyzed by meta-analysis. The random-effects summary relative risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT was 1.98 (95% confidence interval, 1.77-2.22). CONCLUSION(S): The risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT is twice that of natural conceived pregnancies.

A prospective study of stress among women undergoing in vitro fertilization or gamete intrafallopian transfer.

OBJECTIVE: To evaluate whether baseline or procedural stress during in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) affects pregnancy or live birth delivery rates. DESIGN: Prospective study. SETTING: Seven clinics in Southern California between 1993 and 1998. PATIENT(S): One hundred and fifty-one women completed two questionnaires. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The number of oocytes aspirated and fertilized, the number of embryos transferred, the achievement of a pregnancy, live birth delivery, and infant outcomes. RESULT(S): Positive-affect negative-affect score at baseline negatively influenced the number of oocytes retrieved and embryos transferred. A higher expectation of pregnancy was associated with greater numbers of oocytes fertilized and embryos transferred. At baseline, the risk of no live birth was 93% lower for women who had the highest positive-affect score compared to those with the lowest score. Furthermore, the score on the Infertility Reaction Scale was related to negative outcomes in live birth delivery, infant birth weight, and multiple births. During the time of the procedure, the PANAS and Bipolar Profile of Moods States results were related to the number of oocytes fertilized and embryos transferred; stress did not affect pregnancy or delivery. CONCLUSION(S): Baseline (acute and chronic) stress affected biologic end points (i.e., number of oocytes retrieved and fertilized), as well as pregnancy, live birth delivery, birth weight, and multiple gestations, whereas (procedural) stress only influenced biologic end points.

Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis.

BACKGROUND: Few studies have described the perinatal risks associated with infertility, other than for infertility treated by in-vitro fertilisation or gamete intrafallopian transfer. The aim of this analysis was to estimate the risks of perinatal death associated with treated and untreated infertility. METHODS: A population-based case-control study of perinatal deaths was carried out in Leicestershire Health District over the period 1990-94, during which 60,922 babies were delivered. Of these, 567 perinatal deaths were associated with 542 women. 972 mothers were randomly selected as controls. Medical, obstetric, and social data were collected for cases and controls from the medical notes and interviews with the women. The relative risks of perinatal death associated with treated and untreated infertility before the index pregnancy were estimated as odds ratios by means of unconditional logistic regression analysis. FINDINGS: 65 (10%) of cases and 34 (3.5%) of the controls had infertility before the index pregnancy. History of infertility in the index pregnancy, irrespective of treatment, increased the risk of perinatal death (odds ratio 2.9 [95% CI 1.8-4.5]). The population attributable risk fraction for perinatal death related to infertility was 6.2% (3.4-9.0). 45 (54%) of the deaths, even in the untreated group, were associated with immaturity. Compared with women without infertility, women with untreated infertility were at increased risk of perinatal death (3.3 [1.6-6.8]). The risk of perinatal death associated with multiple births did not explain this finding. Similarly, treated infertility also increased the risk of perinatal death (2.7 [1.5-4.7]); the risks associated with multiple births explained some, but not all, of this excess. In Leicestershire, the overall underlying risk of a mother experiencing at least one perinatal death over the study was 9.0 per 1000 women. For women who experience infertility, this risk increases by about 18 per 1000 (6-30). INTERPRETATION: Counselling for women before any form of infertility treatment should include discussion of the risks of perinatal death. Our results would benefit from confirmation. However, we advocate that at antenatal booking a history of infertility, irrespective of treatment, should be sought, because these women have a significantly increased risk of perinatal death, particularly associated with prematurity.

Hydatidiform moles associated with multiple gestations after assisted reproduction: diagnosis by analysis of DNA fingerprint.

In spite of the widespread use of assisted reproductive technology, there have been, to our knowledge, only two reported cases of molar pregnancies after gamete intra-Fallopian transfer and five reported cases after in-vitro fertilization and embryo transfer. We report here a case of a complete hydatidiform mole in a twin pregnancy after gamete intra-Fallopian transfer, as well as a case of a complete hydatidiform mole in a triplet pregnancy after in-vitro fertilization and embryo transfer. The genetic constitution of each conceptus was determined by examination of the restriction fragment length polymorphism of the DNA with four different single-locus probes. This analysis revealed that both hydatidiform moles were of androgenetic origin and probably of monospermic origin. Moreover, the analysis confirmed that the pregnancies were dizygotic and trizygotic pregnancies respectively. The diagnostic utility of the analysis of DNA polymorphism is discussed in cases of a molar pregnancy with coexisting fetuses.

[Mid- and long-term outcome of 77 triplets and their families]. / Devenir à moyen et long-terme de 77 fratries de triplés et de leurs familles.

OBJECTIVE: To compare the family status and neurodevelopment of triplets conceived by spontaneous pregnancy (SP), ovarian stimulation (OS), in vitro fertilization (IVF), and gametal intra-fallopian transfer (GIFT). DESIGN: A follow-up study consisted of neurodevelopmental examination and/or of interviews of parents/pediatricians/teachers and social workers. Outcome of the children was categorized as defective (mild, moderate, severe) or normal. SETTING: The Port-Royal neonatal unit and follow-up clinic. SUBJECTS: From 1/01/1987 to 31/12/94, one to all three neonatal triplets were admitted to the Port-Royal neonatal unit. Pregnancy was SP in 12, OS in 24, IVF in 36, GIFT in 5. All survivors (36 SP, 68 OS, 98 IVF, 14 GIFT) were included and their outcome (at 3 to 10 years of age) was known in 75 families. RESULTS: Prematurity < 32 weeks was highest in the SP pregnancies, with no birth > 37 weeks, and more small-for-dates babies. As of this writing, the neurodevelopmental status was normal or included only a mild deficit (mainly visual corrections) in 82% of SP survivors, 94% of OS survivors, 98% of IVF survivors, all 14 GIFT survivors. Moderate and major deficits were found in one or two siblings of 7 sets of triplets, 5 of which were born < 32 weeks (1 SP, 3 OS, 1 IVF). In all groups, family status was characterized by the need to move, financial problems, maternal exhaustion and parental breakdowns. Five OS mothers, 5 IVF mothers, and one GIFT mother each had one to three subsequent SP pregnancies. In 1997, all families included one to eight children. Because of the cumulative effect of losses, deficits, and other post-natal difficulties, only one of four families had no problems. CONCLUSION: The overall outcome of surviving triplets is good but they are both a prenatal and post-natal hardship for the parents, chiefly the mother. We advocate a more cautious use of OS, no triple implantation at the first IVF, and more social help and guidance for the families during the pregnancy and the first 3 years of life of the triplets.

Births after transcervical gamete intrafallopian transfer with a falloposcopic delivery system.

OBJECTIVE: To evaluate the safety and efficiency of a new delivery system to perform transcervical GIFT. DESIGN: Evaluation of pregnancy rate (PR), miscarriage rate, ectopic pregnancy rate, and delivery rate. SETTING: Institute of Obstetrics and Gynecology, Reproductive Endocrinology Unit, Infertility and IVF Center. PATIENT(S): Twenty-five patients with patent tubes documented by laparoscopy plus falloposcopy. INTERVENTION(S): Superovulation was induced with GnRH analogue and FSH. Under laparoscopic control, transcervical cannulation of the tube was done using a linear everting catheter incorporating direct falloposcopic vision of the tubal lumen. Two lengths of everting catheter (3 and 6 cm) were used providing either isthmic-ampullary or midampullary placement of the inoculum. A comparison was done in terms of ease of access and transfer, falloposcopic observations, and PRs between the groups. MAIN OUTCOME MEASURE(S): Efficacy was established by evaluating the PR, miscarriage rate, ectopic pregnancy rate, and delivery rate. RESULT(S): The PR was 28% (with no differences between the lengths of everting catheters). No ectopic pregnancies occurred. The abortion rate was 28.6% and the delivery rate was 20%. Neither tubal perforation nor other complications occurred during the procedure. CONCLUSION(S): Falloposcopic GIFT is safe and efficient and may be a less invasive alternative than laparoscopic transfer.

Gestaçäo ectópica cornual após GIFT: resoluçäo com uso de metotrexate / Cornual ectopic pregnancy after GIFT: resolution with methotrexate

A incidência de gravidez ectópica (GE) está aumentada em pacientes inférteis submetidas à fertilizaçäo in vitro (FIV). A elevada frequência de alteraçöes tubárias observadas nestas mulheres é determinante principal da nidaçäo anormal. A grande maioria das GE localiza-se na porçäo ampolar da tuba, entretanto, gestaçöes cornuais têm sido descritas após FIV. Atualmente, o tratamento clínico da GE substitui a cirurgia em grande parte dos casos. Apresentamos a seguir, um caso de gestaçäo cornual resultante da transferência intra-tubária de gametas(GIFT), com ótima evoluçäo após uso de metotrexate.

Ovarian hyperstimulation syndrome.

A case of severe ovarian hyperstimulation syndrome (OHSS) prompted us to review our experience of the condition, and to critically evaluate its clinical associations and treatment. Severe OHSS complicated 1.8% of gamete intra-Fallopian transfer (GIFT) cycles, but none of the ovulation induction and artificial insemination by husband (OI/AIH) cycles. It is difficult to establish whether the higher pregnancy rate observed with OHSS was attributable to pregnancy increasing the risk of OHSS, or if it was the development of OHSS which increased the likelihood of pregnancy. Monitoring serum oestradiol levels and ultrasonographic evaluation of growing follicles may be helpful in identifying women at risk. Strategies for reducing the risk of developing severe OHSS were considered.

Embarazo heterotópico asociado a inducción de ovulación: su dificultad diagnóstica / Heterotopic pregnancy associated to ovulation induction: diagnostical difficulty

El embarazo heterotópico (embarazo intrauterino y extrauterino simultáneo), debe ser siempre investigado en todas las pacientes sometidas a inducción de ovulación con o sin técnicas de fertilización asistida. El embarazo heterotópico debe ser sospechado clínicamente y no descartado pese a la presencia de un embarazo intrauterino, a un ascenso normal de la subunidad beta de gonadotrofinas o a una ecografía con imágenes de apariencia normal a nivel anexial. Esto nos permitirá evitar un diagnóstico tardío con la morbilidad asociada que ello implica (salpingectomía) así como la mortalidad en casos excepcionales

Embarazo heterotópico asociado a inducción de ovulación: su dificultad diagnóstica / Heterotopic pregnancy associated to ovulation induction: diagnostical difficulty

El embarazo heterotópico (embarazo intrauterino y extrauterino simultáneo), debe ser siempre investigado en todas las pacientes sometidas a inducción de ovulación con o sin técnicas de fertilización asistida. El embarazo heterotópico debe ser sospechado clínicamente y no descartado pese a la presencia de un embarazo intrauterino, a un ascenso normal de la subunidad beta de gonadotrofinas o a una ecografía con imágenes de apariencia normal a nivel anexial. Esto nos permitirá evitar un diagnóstico tardío con la morbilidad asociada que ello implica (salpingectomía) así como la mortalidad en casos excepcionales (AU)

In vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination: efficacy and potential health hazards on babies delivered.

OBJECTIVE: The purpose of this article was to review the efficacy and potential hazards of assisted conception. STUDY DESIGN: A review of pertinent scientific articles published in English was done. RESULTS: There are no adequate prospective, randomized, controlled, or comparative studies of sufficient power on the efficacy of in vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination in well-defined infertile couples. In vitro fertilization can overcome tubal sterility. The pregnancy per cycle is 19.8% and delivery per cycle is 16.0% for in vitro fertilization (all indications) and 29.5% and 19.8%, respectively, for gamete intrafallopian transfer. In limited prospective studies, in vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination have similar fecundity. Multiple births from in vitro fertilization and gamete intrafallopian transfer are increased, whereas preterm labor and low-birth-weight babies are significantly more common, even in singletons. CONCLUSION: The efficacy or relative superiority of IVF, gamete intrafallopian transfer, and superovulation with intrauterine insemination in nontubal subfertility remains to be shown by properly designed, prospective, randomized, controlled, or comparative studies. Therefore less invasive and less expensive methods such as expectant management or superovulation with intrauterine insemination should be used before embarking on in vitro fertilization and gamete intrafallopian transfer. Further studies on the outcome of babies delivered after assisted conception are required.

What factors predetermine the risk of having a high-order multiple pregnancy with gamete intra-fallopian transfer?

Limiting the number of oocytes transferred at gamete intra-Fallopian transfer (GIFT) has limited the incidence of high-order pregnancy but at the same time compromised the fertility potential of some patients. A review of 300 patients who have undergone GIFT using a flexible approach as to the number of oocytes transferred identifies the patients at risk of high-order pregnancy as those aged under 30 years in whom more than six oocytes are returned and whose partner's spermatozoa have high progressive motility.

Assessing congenital anomalies after preimplantation genetic diagnosis.

BACKGROUND: Preimplantation genetic diagnosis is an exciting advance in prenatal diagnosis. However, the safety of embryo biopsy must be determined with respect to both pregnancy rate and cogenital anomalies. ANALYSIS: Too few pregnancies have been reported to allow meaningful inferences to be drawn, for which reason data on pregnancy losses and anomalies after conventional IVF were first reviewed. Loss rates are approximately 25%, and anomaly rates are not increased over that observed in the general population. Unfortunately, considerable methodological problems exist in published surveys: lack of proper controls, failure to take into account potential confounding variables, anomaly surveillance that is inconsistent with respect to the vigor with which anomalies are sought, inclusion or exclusion of minor anomalies, inclusion or exclusion of anomalies evident only on ultrasound, and even inclusion or exclusion of anomalies present in terminated pregnancies. We recommend prospective surveillance for major anomalies, defined as those causing death, major handicap or requiring surgery. Prospective surveillance ideally dictates collection of intake information at the time pregnancy is diagnosed, surveillance during pregnancy to exclude teratogenic influences, and systematic neonatal anomaly surveillance.

Factors associated with improving success rates with gamete intrafallopian transfer under thin-needle spinal anesthesia.

PURPOSE: In order to reduce the risk of major anesthetic complications associated with laparoscopic gamete intrafallopian transfer procedures, we have exclusively used thin-needle spinal anesthesia over the years 1991 - 1994. This paper will review complication rates in order to further establish the safety profile of GIFT under thin-needle anesthesia and report the changes in our GIFT protocol from 1991 to 1994 which have been associated with a statistical improvement in the implantation rate from 11% to 23% (P = 0.01) and an increase in delivery rates from 29% to 42% per transfer procedure. METHODS: Sixty-eight laparoscopic GIFT procedures were done in women with at least one patent oviduct and failure to respond to less invasive treatment. Clinical variables were analyzed to determine if similar patient populations had been treated over the study period. RESULTS: The improved delivery rates and implantation rates could not be explained by patient selection. No major perioperative complications occurred. Minor perioperative complications and difficulties included one patient requiring general anesthesia, one patient developing a spinal headache which could be managed conservatively at home, and one patient requiring a minilaparotomy to complete the GIFT procedure. The more serious complications occurred as a result of the superovulation and multiple oocyte transfer rather than the surgical or anesthetic technique. These included two patients with severe ovarian hyperstimulation requiring hospitalization, and five delivered triplet pregnancies. Factors associated with improving success rates included improvements in semen and equipment preparation as well as an increase in the number of sperm transferred from 200,000 to 500,000. CONCLUSIONS: GIFT can be performed with relative safety under thin needle spinal anesthesia with high implantation and delivery rates if care is made to optimize sperm and equipment preparation. GIFT under thin-needle spinal anesthesia may be an attractive alternative for treatment of longstanding nontubal infertility in couples willing to take the risk of ovarian hyperstimulation and multiple pregnancy.

Ovarian hyperstimulation syndrome with minimal ascites and massive pleural effusion: report of a case.

A 30-year-old woman was admitted to the hospital due to bilateral massive pleural effusion and right lung collapse with severe respiratory distress. She had been undergoing gamete intrafallopian transfer (GIFT) following three years of primary infertility. Ovarian stimulation was done with pure follicle stimulating hormone (FSH) and human menopausal gonadotropin (hMG) under pituitary suppression with leuprolide acetate. Bilateral chest pain and progressive dyspnea occurred six days after preovulatory oocytes with washed motile sperms were transferred laparoscopically to the fallopian tubes. Chest radiography, sonography and computed tomography revealed a massive right pleural effusion with right lung collapse, and a mild left pleural effusion. Abdominal sonography revealed minimal ascites. Supportive therapy including fluid supply and albumin infusion failed to improve the respiratory distress. A tube thoracostomy was performed, resulting in rapid reexpansion of the lung. The respiratory distress improved markedly after drainage of 6,800 mL of pleural effusion over 7 days. Massive serosanguineous pleural effusion with minimal ascites is unusual in ovarian hyperstimulation syndrome (OHSS). Tube thoracostomy is a safe and effective treatment for massive pleural effusion and lung collapse in the case of OHSS.