High-order Multiple Pregnancies Research Articles

Elective transfer of two embryos on day 3 in good prognosis patients reduces triplet rate without detectable compromise of pregnancy rate

Background and Significance: Reducing the risk of multiple pregnancy, particularly high order multiple pregnancy, is an important challenge to address. Blastocyst transfer of 2 embryos is one option that has been suggested to reduce the risk of high order multiples. However, blastocyst culture has been associated with a higher risk of monozygotic twinning, particularly in a setting in which both transferred embryos have implanted and triplets result.

Monochorionic triplet gestation following in vitro fertilization using donor oocytes: case report

Background and Significance: The multiple pregnancy rate following assisted reproductive technology (ART) is greatly increased over that of spontaneously conceived pregnancies. In recent years, many authors have shown that the rate of monozygotic twinning is also increased, and multiple mechanisms for this rise have been proposed. However, the number of monozygotic high-order multiple pregnancies remains very small.

Elective transfer of two embryos on day 3 in good prognosis patients reduces triplet rate without detectable compromise of pregnancy rate

Background and Significance: Reducing the risk of multiple pregnancy, particularly high order multiple pregnancy, is an important challenge to address. Blastocyst transfer of 2 embryos is one option that has been suggested to reduce the risk of high order multiples. However, blastocyst culture has been associated with a higher risk of monozygotic twinning, particularly in a setting in which both transferred embryos have implanted and triplets result.

Monochorionic triplet gestation following in vitro fertilization using donor oocytes: case report

Background and Significance: The multiple pregnancy rate following assisted reproductive technology (ART) is greatly increased over that of spontaneously conceived pregnancies. In recent years, many authors have shown that the rate of monozygotic twinning is also increased, and multiple mechanisms for this rise have been proposed. However, the number of monozygotic high-order multiple pregnancies remains very small.

What is the most relevant standard of success in assisted reproduction? The importance of informed choice.

Whilst there is a need to emphasize the birth rates of healthy infants when reporting success rates following infertility treatment, is 'the singleton term gestation per cycle started' the most appropriate measure? Although there are many ways to measure the efficacy of medical intervention, none of these exclude from the 'successes' those in whom complications have occurred. The safe delivery of healthy twins at term, while possibly not the ideal outcome, should still be regarded as a treatment success. Although multiple pregnancy, in particular high order multiple pregnancy, continues to be a major problem associated with assisted reproductive treatments and also with ovulation induction, appropriate counselling concerning the risks of twin and triplet pregnancies will allow couples to make informed choices and allow clinicians to continue to individualize treatment plans.

"I couldn't think that far": infertile women's decision making about multifetal reduction.

In this phenomenological study women's experiences regarding their decisions to undergo or forgo multifetal reduction of their higher-order multiple pregnancies were explored. Seven women who had conceived higher-order multiple pregnancies as the result of in vitro fertilization were interviewed. Four participants accepted reduction, whereas three participants declined. Three themes were discerned: (a) the presence of infertility as a barrier to contemplating hyperfertility; (b) multiple-birth pregnancy as yet another form of loss for infertile women; and (c) the lasting effects of having made the decision.

Clomiphene citrate intrauterine insemination (IUI) before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancies

Objective To determine if previous treatment with clomiphene citrate intrauterine insemination (CC-IUI) affects pregnancy and high-order multiple pregnancy (HOMP) rates in subsequent hMG-IUI or FSH-IUI cycles. Design Retrospective cohort study. Setting Private infertility clinic. Patient(s) Five hundred fifty-one patients (age <38 years) without tubal factor infertility, treated with 918 cycles of hMG/FSH-IUI after one or more unsuccessful cycles of CC-IUI; 908 patients treated with 1459 cycles of hMG/FSH-IUI without prior CC-IUI. Intervention(s) CC-IUI, hMG-IUI, FSH-IUI. Main outcome measure(s) Pregnancy rate per cycle, HOMP (three or more gestational sacs). Result(s) Pregnancy rates during the first three hMG-IUI or FSH-IUI cycles averaged 21.8 ± 1.1% without previous CC-IUI, 19.6 ± 1.3% after one to four cycles of CC-IUI, and 3.6 ± 2.6% after ≥ five previous CC-IUI cycles. The HOMP rates were 8.8% without previous CC-IUI, 7.5% after one, 5.7% after two and <2.6% (0 out of 38) after ≥ three previous CC-IUI cycles. Conclusion(s) Pregnancy rates in hMG/FSH-IUI cycles are significantly reduced after four unsuccessful CC-IUI cycles. High-order multiple pregnancies due to hMG/HMG-IUI are reduced following previous unsuccessful CC-IUI cycles.

The desire of infertile patients for multiple births

Objective To determine the proportion of infertile women who prefer a multiple birth over a singleton, patient characteristics associated with this desire, and patient knowledge about the risks of multiple births. Design Prospective analysis. Setting Academic university hospital–based infertility center and private general gynecology clinic. Patient(s) Four hundred sixty-four female patients with infertility who presented for their initial visit. Main outcome measure(s) Demographic characteristics, infertility history, desire regarding multiple births, knowledge of the risks of multiple births, and goals of infertility evaluation and treatment were determined by using a 41-question survey. Univariate analysis was performed to assess patient characteristics associated with the desire for multiple births. Independent factors associated with this desire were assessed by multivariable logistic regression analysis. Result(s) 20.3% of women desired multiples over a singleton gestation. Nulliparity, lower family income, younger patient age, prior evaluation for infertility, longer duration of infertility, and lack of knowledge regarding risks of twin gestations were associated with this desire. Only nulliparity and lower family income were independently associated. Conclusion(s) A sizable minority of infertility patients prefers a multiple birth as their treatment outcome. Patient education may be an effective strategy to reduce the incidence of twin and higher-order multiple pregnancies.

Selected single blastocyst transfers maintained pregnancy outcome and eliminated multiple pregnancies.

Background: Transfer of more than one embryo following in vitro fertilization/intracytoplasmic sperm injection cycles have increased pregnancy rate at the cost of increasing the incidence of triplets and twins. It has been proposed that prolonged culture to the blastocyst stage would automatically result in the selection of good quality embryos for transfer and minimize the incidence of triplets and twins. Methods and Results: The objectives of the present retrospective analysis were to examine the pregnancy outcome, multiple pregnancy and related data following: (i) single blastocyst transfer (BT) and double BT; (ii) single BT in patients belonging to different age groups; and (iii) good, fair or poor quality of BT. A total of 260 BT were carried out between August 1998 and July 2002 and they are included in the current study. Sixty of the 260 BT patients received a single BT, and 41 of them received selected single good quality BT (SSBT). The implantation rate has no significant difference between following single BT (53.3%) and double BT (42.8%). No multiple pregnancy occurred following single BT, while significantly higher (P<0.05) multiple pregnancy rate was observed following a double BT (45.8%). The clinical pregnancy and implantation rates following a single BT were similar (P>0.05) in patients belonging to <30years (62.5%), 30-34years (57.9%) and 35-39years old (35.8%). Conclusion: Selected single good quality BT maintained pregnancy and avoided multiple pregnancies. It is recommended for patients with a risk for high-order multiple pregnancy. (Reprod Med Biol 2004; 3: 13-18).

Complications in High Order Multiple Pregnancies

Purpose: In this retrospective study 43 pregnancies with high order multiples (triplets and quadruplets) were analysed. Results: The most prevalent complication in this cohort of 38 triplet and 5 quadruplet pregnancies was premature labour (74.4%). Patients came for delivery to the hospital in only 14% of pregnancies - in the other 86% patients were sent to the hospital already days or weeks before delivery because of a higher pregnancy risk. In 58.1% of cases anemia was diagnosed before delivery. After a median of 15 days children were delivered in the 32 + 5 week of gestation (median). All children were born premature. 18.6% of patients received transfusions due to anemia, in 72.1% prostaglandins were administered due to atonia. Furthermore, 11.6% of patients were transferred to an intensive care unit, one patient died due to severe HELLP syndrome. The mean birth weight of 114 triplet and 20 quadruplet children was 1575 g (median). 118 children were referred to a neonatal intensive care unit. With respect to perinatal complications 47.8% of children showed respiratory distress syndrome, 10.5% had intracranial bleeding. Follow-up data could be collected from 51 out of 124 surviving children. In 9.8% of these cases a severe disability was diagnosed. In total, 18.6% of all families were affected by at least one dead child or by at least one child with a severe disability. Conclusion: Neonatal morbidity as well as maternal data are comparable to data from other, similiar cohorts. Data regarding neonatal outcome show additional risks compared to singleton pregnancies. Since the gestational age at delivery of high order multiples did not change during the last decades, good success rates could be achieved regarding perinatal mortality. However, the best and optimal approach is the avoidance of high order multiple pregnancies as well as of multiple pregnancies in all assisted reproductive procedures and all procedures with ovulation induction. Strategies are discussed, which might be helpful to achieve this goal.

Stimulated Intrauterine Insemination: Efficient, cost-effective, safe?

A retrospective report of pregnancy and birth rates achieved in 1010 cycles of stimulated intrauterine insemination (SIUI). Over the years there has been an increasing emphasis on safety, particularly towards reducing the number of high order multiple pregnancies. SIUI is a complex form of assisted conception and requires a high level of clinical judgement to maintain an optimal balance between maximising pregnancy and birth rates and minimising complications, of which the most serious is multiple pregnancy. Extrapolating from these results, it is concluded that a well managed SIUI programme that selects patients appropriately, monitors them intensively and has in place effective strategies to manage over-responders safely, should be able to deliver at least a 15% live birth rate per cycle started with only a 5% cycle cancellation rate. Although SIUI birth rates are lower than IVF rates, the much lower cost of SIUI means that this treatment can be more cost-effective than IVF. However SIUI remains more risky than IVF and, despite careful management, high order multiple pregnancy rates will occasionally occur. It is estimated that the rate of unavoidable high order multiple pregnancies (triplets and above) is 4 per 1000 cycles started.

Management of high order (three or move) multiple pregnancy in Osaka Medical Center for MCH

Management of high order (three or move) multiple pregnancy in Osaka Medical Center for MCH

Expression of sHLA-G in supernatants of individually cultured 46-h embryos: a potentially valuable indicator of ‘embryo competency’ and IVF outcome

A retrospective cohort study was conducted on 201 women aged 28–44 years, each of whom underwent one cycle of IVF–embryo transfer with fresh, intracytoplasmic sperm injection (ICSI)-derived 7- to 10-cell embryos, transferred 72 h after oocyte retrieval. Samples of media surrounding separately cultured embryos were collected 46 h post-ICSI and stored for subsequent specific enzyme-linked immunosorbent assay. A total of 594 embryos (from own or donor oocytes) were transferred to 201 women. Group A comprised 159 recipients under 39 years and group B compromised 42 recipients aged 39–44 years. Groups A-1 and B-1 recipients had at least one embryo that tested above the geometric mean for soluble human leukocyte antigen-G (sHLA-G) (‘positive expression’) transferred. In groups A-2 and B-2, all embryos transferred expressed sHLA-G below the geometric mean (‘negative expression’). In group A-1, 72/101 women (71%) achieved ultrasound confirmed (clinical), viable (cardiac activity observed) pregnancies. The implantation rate per embryo (IR) was 38%. In group A-2, 13/58 (22%) achieved viable clinical pregnancies. The IR was 9%. In group B-1, the viable clinical pregnancy rate was 52% (15/29) and the IR was 25% compared with a viable clinical pregnancy rate of 15% (2/13) and an IR of 5% in group B-2. The results of this study suggest that by selecting specific embryos for transfer based on their individual sHLA-G expression, pregnancy and implantation rates can be maximized while the number of embryos transferred can be reduced, thereby minimizing the incidence of high-order multiple pregnancies.

177HYSTEROSCOPIC BLASTOCYST IMPLANTATION A NOVEL EMBRYO TRANSFER PROCEDURE

Various techniques using different types of catheters have been advocated to increase pregnancy rates while reducing side effects from the embryo transfer procedure. However, all of these techniques are ‘blind’ procedures of catheter introduction into the uterus, and the problems of ‘lost embryos’ and the occurrence of ectopic pregnancies persist. A novel hysteroscopic-guided direct embryo transfer procedure with visually directed embryo implantation was developed to improve the current ‘blind’ embryo transfer procedures by increasing chances of success while eliminating tubal pregnancies and decreasing high-order multiple pregnancies from IVF related techniques. At West Coast Infertility Medical Clinic, 57 patients with average age of 28.43±4.54 were analyzed. Stimulation method: controlled ovarian hyperstimulation was initiated with Follitropin β; (Follistim®, Organon Pharmaceuticals, Inc.). Premature endogenous gonadotropin surge (i.e. the prevention of an LH surge) was controlled with ganirelix acitate (AntagonTM, Organon Pharmaceuticals, Inc., West Orange, NJ, USA.). Oocyte retrieval was performed in an office setting under local anesthesia and mild sedation, followed by routine IVF/ICSI, IVC. By Day 5–6, up to 2 best quality blastocyst stage embryos were transferred to patient’s uterus by ‘hysteroscopic embryo implantation’ procedure: a lightweight hybrid (rigid/flexible) mini hysteroscope (Napoli, Inc., Los Angeles, CA, USA) was used for visualization of the endometrial cavity. The scope incorporates a flexible distal end of 3mm in diameter with a straight-through operating channel. In addition, the optic filter is directly connected to a light source, decreasing the weight of the scope and giving a better feel for the scope. The transfer catheter (Napoli, Inc.) is polycarbon based with a tapered tip (to 500μm), beveled to 60°. During embryo transfer procedure, the catheter tip was inserted into a depth of 1mm from the surface of the endometrium under direct hysteroscopic visualization. The loaded embryos with 10μL medium was released underneath the endometrium to produce a ‘bubble’ cushion. Luteal phase support was provided (3000IU of hCG at Day 3 and Day 6 post-retrieval, separately). Pregnancies were determined by serum hCG concentration of 5IUmL−1 or more at Day 16 post-retrieval. Thirty out of 57 (52.6%) women became pregnant. Multiple pregnancy rate was 4 out of 30 (13.3%) and comprised only of twins, and no ectopic pregnancy was found. In conclusion, a newly developed instrument and embryo transfer procedure by mechanical implantation of the embryo was achieved. By implanting the embryos, we have reduced the number of embryos that are transfered, minimized the chances of ‘losing’ embryos, and eliminated ectopic pregnancies.

Gonadotrophin ovarian stimulation and intrauterine insemination for unexplained infertility

Over the past 15 years, there has been a marked increase in the use of ovulation induction and intrauterine insemination (IUI) for the treatment of unexplained infertility. However, although ovulation induction and IUI have rapidly gained popularity, clinical use is based largely on practical experience rather than on well-designed scientific studies. This article summarizes the evidence in this area. Despite clinical heterogeneity and different methodological qualities of the trials, it can be concluded that ovulation induction significantly improves the probability of conception in couples with unexplained infertility, particularly when associated with IUI. It is remarkable, though, that there has been only one large-scale, randomized trial of ovulation induction plus IUI in the treatment of unexplained infertility in which one of the study arms is an untreated control group. For couples requiring treatment, the complication rate must be minimized, particularly the occurrence of high-order multiple pregnancy. Evaluation of the effectiveness and safety of low-dose gonadotrophin administration in patients with unexplained infertility is limited and further studies are warranted.

Toward single embryo transfer policy

Toward single embryo transfer policy

Prevention of Multiple Pregnancy During Ovulation Induction

Gonadotrophin ovulation induction is currently used for a heterogeneous group of ovulation disorders and unexplained infertility. In the United States it is reported that multiple pregnancy rates of greater than 30% occur as a result of ovulation induction, most commonly after controlled ovarian hyperstimulation and intrauterine insemination. Treatment strategies to reduce the incidence of multiple pregnancies on ovulation induction programs can be targeted to reducing multiple follicular development and subsequent ovulation by a more aggressive cancellation policy, follicle reduction by fine needle aspiration or conversion to IVF; or dealing with the problem of multiple gestation after it has occurred (i.e., multifetal pregnancy reduction). The procedures and abilities exist to resolve this problem. What is needed are appropriate treatment guidelines and well constructed trials to demonstrate that higher order multiple pregnancies can be substantially reduced and/or eliminated without compromising a couple's chances to conceive.

Prevention of Multiple Pregnancy During Ovulation Induction

Gonadotrophin ovulation induction is currently used for a heterogeneous group of ovulation disorders and unexplained infertility. In the United States it is reported that multiple pregnancy rates of greater than 30% occur as a result of ovulation induction, most commonly after controlled ovarian hyperstimulation and intrauterine insemination. Treatment strategies to reduce the incidence of multiple pregnancies on ovulation induction programs can be targeted to reducing multiple follicular development and subsequent ovulation by a more aggressive cancellation policy, follicle reduction by fine needle aspiration or conversion to IVF; or dealing with the problem of multiple gestation after it has occurred (i.e., multifetal pregnancy reduction). The procedures and abilities exist to resolve this problem. What is needed are appropriate treatment guidelines and well constructed trials to demonstrate that higher order multiple pregnancies can be substantially reduced and/or eliminated without compromising a couple's chances to conceive.

Fallopian tube sperm perfusion: the impact of sperm count and morphology on pregnancy rates.

To evaluate the effect of changed criteria for sperm count and morphology when performing fallopian tube sperm perfusion (FSP) in unexplained infertility. We report on a longitudinal study in which two periods of insemination cycles are compared. One hundred and eighty-three couples who started 361 stimulation cycles intended for FSP were included in the first period and 190 couples starting 303 cycles in the second period. The sperm requirement in the first study period was at least 7 million sperm in the prepared test sample. The FSP cycle included downregulation, controlled ovarian hyperstimulation (COH), ovulation induction and intrauterine and intrafallopian tube insemination using a sperm suspension of 3 mL volume. To avoid high-order multiple pregnancies, cycles at risk were converted to in vitro fertilization (IVF). Based on the results from the first period, sperm requirements were lowered to a sperm count of 3 million and at least 5% normal morphology according to strict criteria. FSP was performed in 51% and 60% of started cycles during the two periods with similar pregnancy (24% and 23%) and birth (15% and 19%) rates. Neither sperm count nor morphology above the requirements affected pregnancy rates. IVF-converted, completed cycles reached equal pregnancy (41%) and delivery (32%) rates in both periods. Multiple pregnancy rates were higher after IVF (38%) than after FSP (24%). The lowered requirements for sperm count and morphology have not impaired pregnancy results after FSP. Patients who either completed an FSP cycle or had their cycle converted to IVF were all at high risk of multiple pregnancy.

Do prophylactic prostaglandins reduce the transfusion rate at cesarean section in high-order multiple pregnancies?

Objective: Cesarean section is the more usual mode of delivery in high-order multiple pregnancy (≥3). Excessive uterine distension increases the risk of bleeding and the need for transfusion. The aim of this study was to investigate if prophylactic use of prostaglandins at cesarean section for high-order multiple pregnancies reduces blood loss and transfusion requirement based on historic data. Study design: We studied a prospective series of 28 parturients with high-order multiple pregnancy (group 2) who were treated, after clamping the last umbilical cord, with oxytocin (5 IU intravenous then 35 IU in a 24 h infusion) combined with intravenous prostaglandin. A comparable retrospective series of 14 patients (group 1) had been given oxytocin alone at the same dose. Postoperative serum hemoglobin and transfusion rate as well as adverse effects were compared between the two groups. Student’s t-test was used to compare continuous variables. Chi square test and Fisher exact test were used to compare categorical variables. Results: The two groups were comparable for anthropometric data and duration of pregnancy. None of the patients in group 2 required red cell transfusion while 21.4% of those in group 1 required transfusion. A significant lower decrease of postoperative haemoglobin is noted in group 2 ( P=0.0006). Multivariate analysis using variables significant at univariate analysis and pre-eclampsia confirmed this difference. There were no adverse reactions to treatment. Conclusion: In our experience, prophylactic prostaglandin infusion at cesarean section in high-order multiple pregnancy is associated with a lower need for per operative red cell transfusion and a higher postoperative hemoglobin level. This observation merits confirmation in larger studies.