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A randomized trial between GIFT and ovarian stimulation for the treatment of unexplained infertility and failed artificial insemination by donor.

This study was designed to investigate the surplus effect of gamete intra-Fallopian transfer (GIFT) over ovarian stimulation alone, in patients with unexplained infertility. A total of 50 patients with unexplained infertility of at least 3 years duration, or unexplained failure of artificial insemination by donor (AID) for at least 12 cycles, meeting strict inclusion criteria, were randomly selected for either two GIFT cycles or two ovarian stimulation cycles. Ovarian stimulation was combined with timed intercourse, or timed cervical donor insemination. In 38 completed GIFT cycles, five clinical pregnancies (13.2% per cycle) occurred and in 44 ovarian stimulation cycles four clinical pregnancies occurred (9.1% per cycle). Five remaining GIFT cycles were converted into in-vitro fertilization leading to two pregnancies. Of the 50 patients suffering from unexplained infertility, the 23 who did not have AID gave rise to four pregnancies out of 39 cycles (10.3%); from the remaining 27 patients who underwent AID, seven pregnancies were achieved out of 48 cycles (14.6%). No statistical differences between GIFT and ovarian stimulation treatment were found. Therefore, the GIFT success rates can be explained at least in part, if not fully, by the effect of ovarian stimulation alone. Consequently, ovarian stimulation should be considered in unexplained infertility before more elaborate forms of assisted reproduction are used.

Adult↗

Will GnRH antagonists provide new hope for patients considered 'difficult responders' to GnRH agonist protocols?

We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.

Clomiphene↗

Age, pregnancy and miscarriage: uterine versus ovarian factors.

This study was performed to evaluate the relative contribution of oocyte and uterine factors to the age-related reduction in fecundity. The pregnancy and miscarriage rates in women receiving donated oocytes were compared to those in women using their own oocytes in in-vitro fertilization (IVF) and gamete intra-Fallopian transfer (GIFT) procedures. Oocyte donation with embryo transfer was performed on 241 women in 371 cycles; 116 of these women became pregnant (48% per patient and 31.5% per cycle) of whom 40 (35%) miscarried, giving a live birth rate of 20.5%. Assisted conception, in the form of IVF/GIFT procedures, was performed on 1331 women using their own oocytes in 2194 cycles; 627 of these women became pregnant (47% per patient and 28.7% per cycle), of whom 228 (36%) miscarried, giving a live birth rate of 18.2%. Neither the age of the donor nor the age of the recipient was related to pregnancy rate. The age of the donor, however, was directly related to the miscarriage rate. On the other hand, the age of patients undergoing IVF/GIFT was inversely related to the pregnancy rate and directly related to the miscarriage rate. In women of 40 years or over, the overall pregnancy and live birth rates were significantly higher and the miscarriage rate was significantly lower in the group receiving donated oocytes compared to the group using their own oocytes. In summary, we suggest that the age-related decline in fecundity is associated with the age of the oocytes rather than the age of the uterus.

Abortion, Spontaneous↗

The influence of ovarian response on gamete intra-Fallopian transfer outcome in older women.

Fecundity declines with increasing age in women. The pregnancy rate is lower in in-vitro fertilization/embryo transfer (IVF/ET) in women aged greater than or equal to 40 years. We analysed 349 consecutive gamete intra-Fallopian transfer (GIFT) cycles in women aged greater than or equal to 40 years to identify factors which affected the outcome. A maximum of four oocytes were transferred in GIFT as recommended by the Interim Licensing Authority; 61 women (17.5%) had a positive serum beta-human chorionic gonadotrophin, 35 (10%) had a miscarriage and 26 (7.5%) delivered live infants. The pregnancy rate was lower than with younger women while the conception loss was higher. Pregnancy and delivery rates increased as the number of oocytes retrieved increased but declined again if greater than 10 oocytes were retrieved. If 1-3 oocytes were retrieved, the pregnancy rate was 9.7% and the delivery rate was 3.9%; if 4-10 oocytes were retrieved, the pregnancy rate was 22.1% and the delivery rate was 10.1%, and when greater than 10 oocytes were retrieved, the rates were 17.6 and 5.9% respectively. The highest pregnancy rate was when four oocytes were transformed in GIFT (22.4%) and the delivery rate was 10.0%. An adequate response to long down-regulation with gonadotrophin-releasing hormone agonist was also a factor associated with high delivery rates (13.5%). We conclude that the delivery rate after GIFT in women aged greater than or equal to 40 years is low, but there is a subgroup who have an acceptable delivery rate because of a good ovarian response. In this group, pituitary down-regulation improves the outcome of treatment.

Adult↗

In vitro fertilisation. A review of drug therapy and clinical management.

Since the first in vitro fertilisation (IVF) pregnancy was delivered in 1978, this procedure has resulted in thousands of pregnancies and opened a vast new frontier of research and treatment for the infertile couple. Pregnancy rates with IVF improve as the number of high quality embryos available for transfer increases; therefore, ovarian stimulation agents to produce multiple oocysts for IVF are advantageous. Clomifene (clomiphene citrate), human menopausal gonadotrophin (hMG; menotropins), and subsequent generations of products are commonly used as stimulation agents. In conjunction with the stimulation agents, gonadotrophin-releasing hormone (GnRH) agonists and human chorionic gonadotrophin (hCG) serve as adjuvants for successful control of all events in the induction process. Clomifene, an estrogen agonists/antagonist, occupies the estrogen receptor for a longer period of time than estrogen (weeks versus hours). Because this signal is interpreted as low estrogen, GnRH is released, which produces a rise in circulating levels of follicle-stimulating hormone (FSH) and luteinising hormone (LH) and subsequent ovarian follicular development. Menotropins is collected by passing urine from menopausal donors over a Sepharose column, followed by removal of high molecular weight impurities by chromatography. The mixture of FSH and LH is biologically standardised. This product stimulates multiple ovarian follicular development. Urofollitrophin is produced using antibodies to hCG anchored to a separation column. LH then can be excluded from the eluate by binding to the hCG antibodies (LH immunoaffinity column). Highly purified FSH is obtained by passing menopausal urine over a column with monoclonal antibodies to FSH. The isolated FSH is then eluted from the column by a highly basic solution and crystallised. This product delivers FSH at a 90% purity and can be administered subcutaneously rather than intramuscularly. Dosage is standardised on a mg/kg basis. Recombinant human FSH is completely free of LH and offers the advantages of better batch consistency, greater purity, and absence of any human contaminants. It may be given both subcutaneously and intravenously. Genetically engineered FSH combines portions of the native protein with another protein (hCG) which enhances its potency and extends the half-life compared with wild-type FSH. Short, medium and ultra-long activity analogues of genetically engineered FSH may be used to tailor stimulation protocols in various clinical situations. Growth hormone is an adjuvant to ovarian stimulation which results in a decreased number of ampoules of menotropins being required to achieve ovulation in poor responders. Ovulation triggers include both hCG and GnRH agonists. Progesterone supplementation is generally used in the luteal phase of the IVF cycle and is administered by intramuscular injection or vaginal suppository. It appears that conscious sedation with midazolam, pethidine (meperidine) and fentanyl is nontoxic for oocyte recovery. If full anaesthesia is required for gamete intrafallopian tube transfer (GIFT) or zygote intrafallopian tube transfer (ZIFT), balanced anaesthesia with nitrous oxide and an opioid appears to be the most appealing option. Appropriate information on the clinical use of the drugs used in IVF greatly reduces patient stress associated with the complex multidrug regimens associated with the procedure.

Antibiotic Prophylaxis↗

Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF.

PURPOSE: In vitro fertilization (IVF) and to a lower extent gamete intra-fallopian transfer (GIFT) have become routine infertility treatments in industrialized countries. Our purpose is to compare the obstetric and neonatal characteristics of singleton and twin pregnancies after GIFT and IVF with those conceived spontaneously. METHODS: This case-control study was conducted in a tertiary care medical center. The 322 singleton and 78 twin pregnancies after GIFT or IVF from 1991 through 1996 were evaluated and compared with each other, and with a control group that conceived spontaneously and matched for parity, maternal and gestational age. Statistical significance of differences was assessed by chi(2) test or two-tailed Fisher exact test. Continuous variables were compared by the paired t-test. RESULTS: Pregnancy-induced hypertension (PIH) and vaginal bleeding were significantly more frequent maternal complications in the GIFT/IVF singleton groups compared to controls. In twin pregnancies the rate of cesarean sections, vaginal bleeding and preterm labor were more common after GIFT/IVF but did not reach statistical significance. Assisted reproduction was associated with low birth weight only in twin pregnancies when controlled for confounding variables, however perinatal outcome was comparable. There was no significant difference in the outcome measures between GIFT and IVF pregnancies. CONCLUSION: After controlling for parity, maternal and gestational age, singleton pregnancies conceived by GIFT/IVF are at increased obstetrical risk, however the perinatal outcome is comparable despite a lower average birth weight.

Case-Control Studies↗

A prospective study of the effects of female and male caffeine consumption on the reproductive endpoints of IVF and gamete intra-Fallopian transfer.

BACKGROUND: This study evaluated the timing and amount of caffeine intake by women and men undergoing IVF and gamete intra-Fallopian transfer (GIFT) on oocyte retrieval, sperm parameters, fertilization, multiple gestations, miscarriage, and live births. METHODS: A prospective study of 221 couples was conducted in Southern California between 1993 and 1998. "Usual" caffeine intake during lifetime and 1 year prior to attempt, caffeine intake during the week of the initial clinic visit, as well as intake during the week of the procedure, was evaluated from beverages (coffee, soda, tea) and chocolates. RESULTS: Not achieving a live birth was significantly associated with "usual" female caffeine consumption [adjusted odds ratios (95% confidence intervals): 3.1 (1.1, 9.7) and 3.9 (1.3, 11.6) for intake of >2-50 and 50 mg/day, compared with 0-2 mg/day] and consumption during the week of the initial visit [2.9 (1.1, 7.5) and 3.8 (1.4, 10.7)] female compared with 0-2 mg/day, although caffeine use was low. Infant gestational age decreased by 3.8 (-6.9, -0.7) or 3.5 (-6.7, -0.3) weeks for women who consumed >50 mg/day of caffeine "usually" or during the week of the initial visit. The odds of having multiple gestations increased by 2.2 (1.1, 4.4) and 3.0 (1.2, 7.4) for men who increased their "usual" intake or intake during the week of the initial visit by an extra 100 mg/day. Caffeine intake was not significantly associated with other outcomes. CONCLUSIONS: This is the first IVF/GIFT study to report any effect of caffeine on live births, gestational age, and multiple gestations. If these findings are replicated, caffeine use should be minimized prior to and while undergoing IVF/GIFT.

Abortion, Spontaneous↗

Antibiotic treatment based on seminal cultures from asymptomatic male partners in in-vitro fertilization is unnecessary and may be detrimental.

We questioned the policy of routine microbiological culture of semen prior to in-vitro fertilization (IVF) with a view to prescribing antibiotics to reduce the risk of introducing seminal infection into the embryo culture system. An initial retrospective study examined serum microbiology reports of 449 couples undergoing IVF or gamete intra-Fallopian transfer (GIFT). In semen samples taking >/=1 days to reach the microbiology laboratory compared with same-day delivery there was increased frequency of significant culture of enterococci (27 versus 15%, P < 0.01). In samples taking >/=2 days there was increased frequency of significant culture of Gram-negative bacilli (31 versus 12%, P < 0.01) and of overall culture of other potentially pathogenic organisms (26 versus 14%, P < 0.01). We questioned diagnostic accuracy and relevance. Therefore, in a prospective study, semen and high vaginal swabs obtained on the day of oocyte collection were cultured from 100 couples having IVF or GIFT, of whom 52 male partners had been treated with antibiotics following positive pre-IVF semen culture. The presence of bacteria in semen samples used only for IVF (n = 90) did not reduce fertilization rates nor lead to infection of the embryo culture system. However, there was an increased incidence of significant culture of vaginal Gram-negative bacilli in patients with treated partners compared with untreated partners [15/52 (29%) versus 5/48 (10%), P < 0.05]. Thus antibiotic therapy in the male partner may increase the likelihood of inoculation of antibiotic-resistant pathogenic bacteria from the vagina into the embryo culture system during vaginal oocyte collection. In asymptomatic patients, microbiological screening of semen samples prior to IVF treatment and subsequent treatment with antibiotic therapy in those with positive cultures appears to be unnecessary and may be detrimental to IVF outcome.

Adult↗

Gamete intra-fallopian transfer in non-endometriotic pelvic adhesions.

This report presents our experience with gamete intra-Fallopian transfer (GIFT) in cases with non-endometriotic pelvic adhesions. Two-hundred-and-eight GIFT attempts, where pelvic adhesions were identified laparoscopically in patients with no previous history of endometriosis, were subdivided into two groups: (i) post-surgical (n = 134) and (ii) non-surgical (n = 74). The extent of the adhesions was further classified according to the American Fertility Society (AFS) classification system. The overall clinical pregnancy rate was 39.4% (82 out of 208 attempts). There was no significant difference in the clinical pregnancy rate per attempt between the surgical (38.8%) and the non-surgical (40.5%) groups. A gradual, but not significant decline in the pregnancy rate was noticed from adhesion Stages I to III, but Stage IV had a significantly lower pregnancy rate (22.7%) than Stage I (47.4%). The intra-uterine pregnancy rate was observed to be higher, but not significantly, in the non-surgical (37.8%) than in the surgical (29.1%) cases. The overall ectopic pregnancy rate was 7.2% per attempt and 18.3% per clinical pregnancy. In the post-surgical group, the ectopic pregnancy rate per pregnancy was 3.5 times that in the non-surgical (23.2% versus 6.5%, respectively), and it was significantly higher in Stage IV (40%; two out of five pregnancies) than in Stage I adhesions (11.1%; three out of 27 pregnancies). In cases with a history of tubal surgery, the ectopic pregnancy rate was 33.3% (10 out of 30 pregnancies). Our results indicate that GIFT can offer a successful treatment option for selected cases with non-endometriotic pelvic adhesions.

Adult↗

[Mid- and long-term outcome of 77 triplets and their families].

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.

Adolescent↗

Gamete intra-fallopian transfer or intrauterine insemination after controlled ovarian hyperstimulation for treatment of infertility due to endometriosis.

We compared the effectiveness of gamete intra-Fallopian transfer (GIFT) and intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) in the treatment of infertility due to endometriosis. This was a retrospective study carried out at a tertiary teaching medical center. A total of 127 consecutive patients with endometriosis were treated with GIFT or IUI after COH between June 1990 and December 1998. Patients were divided into two groups. Group 1 (n = 97) included patients with stages 1 and 2 endometriosis, and group 2 (n = 30) included patients with stages 3 and 4 endometriosis. Laparoscopic conservative surgery for endometriosis was performed prior to IUI for patients in both group 1 and group 2. In group 1, 55 patients underwent 95 cycles of IUI after COH and 42 patients underwent 57 cycles of GIFT. In group 2, 14 patients underwent 16 cycles of IUI after COH, while 16 patients underwent 22 cycles of GIFT. The stimulation protocol for both GIFT and IUI was mid-luteal pituitary down-regulation with a gonadotropin releasing hormone agonist (GnRH-a) followed by gonadotropins. In group 1, the pregnancy rates (GIFT = 50.9%, IUI = 29.4%) and the delivery rates (GIFT = 28.1%, IUI = 14.7%) per cycle were significantly higher in GIFT compared to IUI (p = 0.009 and p = 0.05, respectively). There was no significant differences in the pregnancy rate (GIFT 69%, IUI 50.9%, respectively) or the delivery rate (GIFT 38.1%, IUI 25.5%) per patient. In group 2, there was no significant difference in the pregnancy rate (GIFT 54.5%, IUI 31.3%) or the delivery rate (GIFT 40.9%, IUI 12.5%) per cycle, but the difference in the pregnancy rate (GIFT 75%, IUI 35.7%) and the delivery rate (GIFT 56.3%, IUI 14.3%) per patient was significantly higher in GIFT compared to IUI (p = 0.04 and p = 0.02, respectively). We conclude that, when the same stimulation protocol is used in the early stages of endometriosis, a few cycles of IUI can achieve similar results to GIFT, and therefore should be used first. In advanced stages of endometriosis GIFT appears to be more effective.

Abortion, Spontaneous↗

Anaesthesia for assisted conception: a survey of UK practice.

A telephone survey was undertaken of all UK centres (total 70) licensed for performing in vitro fertilization (IVF) and gamete intra-fallopian transfer (GIFT) by the Human Fertilisation and Embryology Authority (HFEA). The survey was carried out during the months of November and December 1997. Thirty-seven (52.1%) centres were in the NHS sector and 33 (47.8%) in the private sector. A response was available from 60 (84%) centres. A standard questionnaire was used which requested information about the procedures carried out, anaesthetic technique and pharmacological agents used. Forty-seven centres carried out IVF, two centres GIFT and 11 centres both. Out of 58 centres carrying out IVF, sedation was used in 28, general anaesthesia in 17, sedation combined with regional anaesthesia in seven and regional anaesthesia in one. Five centres gave a choice. Out of 22 centres using general anaesthesia for IVF, 12 used inhalational agents (isoflurane eight, enflurane four, sevoflurane two), eight used total intravenous anaesthesia (TIVA) with propofol and two centres inhalational agents or TIVA. Propofol was the induction agent in all but two centres. For IVF under sedation, 18 centres used midazolam, five used diazepam, three used opioids, one used entonox and the remaining ones a combination. When sedation was combined with regional anaesthesia, four centres used midazolam, two used propofol, one used midazolam with propofol, one used opioids and one used entonox. The regional technique in the 11 centres was either paracervical block with lignocaine (eight) or subarachnoid block with bupivacaine (three). Systemic analgesia was secured with fentanyl (22), pethidine (16), alfentanil (15), diclofenac (14), piroxicam (two), ketorolac (one) and ibuprofen (one). Five centres did not use any opioids; 40 centres did not use any nonsteroidal agents (NSAIDs). Out of the 13 centres that carried out GIFT, 12 used general anaesthesia while the thirteenth gave the patient a choice between general or regional anaesthesia. 11 centres used inhalational agents (isoflurane nine, enflurane two) while two used TIVA with propofol; propofol was the induction agent used in six centres while thiopentone was used in five. The range of analgesics was wide--fentanyl in six centres, alfentanil in three, morphine in two, diclofenac in five and ketorolac in one. Two centres did not use any opioids and seven centres did not use an NSAID. The only agreement at present appears to be that halothane is an unwise choice for IVF. No other technique has yet been proven to be either advantageous or detrimental.

Analgesia↗

Relationship between the results of sperm analysis and GIFT.

In vitro fertilization (IVF) and GIFT have been proposed as therapeutic approaches in infertile couples where a significant male factor is present. To date, few published data are available relating the success rate of GIFT to the severity of the male factor. In this report the results of the first 172 GIFT cases were analyzed. The overall pregnancy rate was 18.0%. The relationship between the occurrence of pregnancy and sperm count (millions/ml), total sperm count (millions/ejaculate), % motility, motile sperm count (millions/ml) and total motile sperm count (millions/ejaculate) were examined. Significant direct correlations were observed between the clinical pregnancy rate and sperm count, total sperm count, motile sperm count and total motile sperm count. Motile sperm count and total motile sperm count had the best correlations with clinical pregnancy rates, which were over 24.0% in groups with motile sperm counts exceeding 40 X 10(6) cells/ml or total motile sperm counts greater than 100 X 10(6)/ejaculate. The clinical pregnancy rates were 12.5% and 7.7%, respectively, for groups with motile sperm counts under 10 X 10(6)/ml and total motile sperm counts below 25 X 10(6)/ejaculate. No correlation was found between percent motile cells and pregnancy rate. Results of the sperm penetration assay using zona-free hamster eggs were available in a subpopulation of 27 patients. No significant correlation between this sperm penetration assay and pregnancy rate could be demonstrated. The incidence of chemical pregnancy showed a significant negative correlation with the total motile sperm count, indicating a higher incidence of early pregnancy wastage in cases of oligozoospermia.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Ethical and legal implications in IVF and prenatal diagnosis in the U.K.

The natural desire for couples to be parents and the medical practitioner's inability to treat most genetic diseases have been responsible for some of the most exciting research into infertility and genetic disorders. This has led in the United Kingdom to the establishment of the Warnock Committee of Inquiry into Human Fertilization and its report in 1984, and to a Review of the guidance on Research Use of Fetuses and Fetal Material published in 1989 and known as the Polkinghorne Report. The Warnock Report, among other ethical issues, considers the most fundamental question which has been debated for thousands of years, namely, What is life and when does it begin? More recently, the report has been responsible for new legislation which imposes ethical and legal restrictions on the scientific and medical community. The Polkinghorne Report recommends a voluntary code of practice which is morally and ethically acceptable within our society. We are also fortunate in the U.K. to have a parliamentary structure which allows debate on such important human issues and is prepared to impose ethical restrictions.

Abortion, Induced↗

Genetic amniocentesis following multifetal pregnancy reduction to twins: assessing the risk.

Fifty-three patients who elected to reduce their pregnancies to a twin gestation in our centre are known to have subsequently undergone genetic amniocentesis. Five of these patients lost entire pregnancy following the genetic amniocentesis procedure. This is equivalent to a 9.4 per cent pregnancy loss rate for reduced twin gestations in comparison with an expected loss rate of 2 per cent for non-reduced twin gestations.

Abortion, Spontaneous↗