Risk of spontaneous preterm birth in IVF-conceived twin pregnancies

Objective: To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester in screening for preterm birth in in vitro (IVF)-conceived twin pregnancies versus spontaneously-conceived twin pregnancies.

Methods: This was a retrospective cohort study. Potential study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7 to 23 6/7-week gestation. All women with twin diamniotic pregnancies screened with a single TVU CL for this trial were included. Mean TVU CLs were compared between IVF-conceived twin pregnancies and spontaneously-conceived twin pregnancies. The relationship of TVU CL with gestational age at delivery was assessed. Incidence of short TVU CL, defined as TVU CL ≤30?mm, was also calculated in the two groups. The primary outcome was the mean of TVU CL. Distribution of CL was determined and normality was examined in both groups

Results: A total of 668 women with diamniotic twin pregnancies who underwent TVU CL screening between 18 0/6 and 23 6/7 weeks were included. 158 (23.7%) were IVF-conceived pregnancies, and 510 (76.3%) were spontaneously-conceived pregnancies. No women received progesterone, pessary, or cerclage for preterm birth prevention during pregnancy. The mean TVU CL was significantly lower in the IVF-conceived group (32.2?±?10.5?mm) compared to the spontaneously-conceived group (34.1?±?9.1?mm) (mean difference (MD)???1.90?mm, 95%CI ?3.72 to ?0.08). The incidence of TVU CL ≤30?mm was 30.4% in the IVF-conceived group and 21.6% in the spontaneously-conceived group (adjusted odds ratio (aOR) 1.59, 95%CI 1.06–2.37). IVF-conceived twins had a significantly higher risk of spontaneous preterm birth <34 weeks (32.9 versus 21.2%; aOR 1.83, 95% confidence interval (CI) 1.23–2.71) and higher rate of delivery due to spontaneous onset of labor (64.5 versus 54.9%; aOR 1.50, 95%CI 1.03–2.17). For any given TVU CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for IVF-conceived twins was earlier by about 1 week on average compared with spontaneously-conceived twins.

Conclusions: The higher rate of spontaneous preterm birth in IVF-conceived twin pregnancies is predicted by lower midtrimester TVU CL, as well as by the lower gestational age at birth per any given CL in the IVF-conceived compared to the spontaneously-conceived twin pregnancies.     

Mild ovarian stimulation for in vitro fertilization: one perspective from the USA

Purpose

To provide a perspective regarding mild ovarian stimulation, taking into account particular issues relevant in the United States

Methods

Literature review and editorial commentary

Results

Mild ovarian stimulation for IVF has some proven and some theoretical advantages over conventional stimulation, such as lower risk of ovarian hyperstimulation syndrome and lower cost per fresh IVF cycle. However, cumulative live birth rate, including transfers from fresh and frozen embryos, is likely to be lower with mild stimulation. The cost-effectiveness of mild stimulation IVF in the United States has not been established.

Conclusions

Mild ovarian stimulation is an appropriate option to consider for certain patient groups or based on patient preference. However, significant potential disadvantages limit its widespread acceptability for patients in the United States at this time.     

成熟卵泡获卵率对体外受精结局的影响

目的比较在体外受精-胚胎移植/卵细胞浆内单精子注射（IVF-ET/ICSI）过程中,控制性超促排卵（COH）后成熟卵泡获卵率对IVF-ET/ICSI的实验室和临床结局的影响。方法回顾性分析2010年5月至2010年12月四川大学华西第二医院行IVF-ET/ICSI治疗的693例患者,共746个周期,根据获卵率将患者分为A组：获卵率≥80%;B组：获卵率50%～79%;C组：获卵率30%～49%;D组：获卵率〈30%。比较4组患者的临床和实验室结局。结果 A、B组卵子成熟率、受精率、卵裂率和可移植胚胎形成率等各项临床和实验室结局比较,差异均无统计学意义（P〉0.05）。随着获卵数的减少,获卵数最低的D组的卵子成熟率、受精率、卵裂率和可移植胚胎形成率与A组和B组比较,差异有统计学意义（P〈0.05）;同时,D组的临床妊娠率、胚胎种植率和累积妊娠率明显低于其他各组（P〈0.05）。C组受精率、卵裂率、可移植胚胎形成率和临床妊娠率也显著低于A组（P〈0.05）,C组卵裂率、临床妊娠率低于B组（P〈0.05）,但C组的累积妊娠率与A组和B组相似（P〉0.05）。结论获卵率减少可导致卵子成熟率、受精率、卵裂率和可移植胚胎形成率下降,直接导致临床妊娠率下降。     

A comparison of maternal and perinatal outcome between in vitro fertilization and spontaneous dichorionic-diamniotic twin pregnancies

Objective: To compare the maternal and neonatal outcome of dichorionic diamniotic in vitro fertilization (IVF) twin and spontaneous twin pregnancies.

Material and methods: Maternal and fetal data of all consecutive dichorionic-diamniotic twin pregnancies delivered in our institution between January 2009 and May 2015 were abstracted from medical records and pregnancy outcome of IVF twin was compared to spontaneous twin.

Results: Overall 708 twin pregnancies (449 IVF and 259 spontaneous) were included. Women in the IVF group were 2 years older and more frequently nulliparous. The rate of pregnancy induced hypertension and preeclampsia (PIH/PET) was three times higher in the IVF group than in the spontaneous group. The rate of preterm births, before 37 weeks of gestation and the rate of cesarean section were higher in the IVF group. These results were confirmed by multivariate analysis. The neonatal outcome was similar in both the groups except for a lower mean newborn birthweight in the IVF group.

Conclusion: Women with IVF twins are at a significantly higher risk of having preterm births, PIH/PET and cesarean section but there was no significant adverse effect on neonatal outcome except for a lower mean newborn birth weight.     

In vitro fertilization and gamete micromanipulation in the lowland gorilla

Purpose Our purpose was to utilize current reproductive technologies to treat an infertile female lowland gorilla.Results Following pituitary down-regulation with a gonadotropin releasing hormone agonist and follicular stimulation with human menopausal gonadotropins, transrectal ultrasound-guided aspiration of ovarian follicles yielded nine oocytes. Following failed fertilization with both epididymal and electroejaculated sperm, zona dissection and sperm injection were performed and produced one embryo, which was cryopreserved. Immature oocytes were obtained from ovarian sections and were either cultured in vitro or cryopreserved.Conclusions This report demonstrates that in vitro fertilization techniques, including pituitary suppression, ultrasound-guided aspiration, micromanipulation, and cryopreservation, can be used to assist reproduction in the lowland gorilla.     

Outcomes of pregnancies achieved by donor egg in vitro fertilization--a comparison with standard in vitro fertilization pregnancies

OBJECTIVE: Prior studies on donor egg in vitro fertilization (DE-IVF) outcomes have been limited by the lack of an appropriate control group. Here, we review the obstetric and perinatal outcomes of pregnancies achieved by DE-IVF and compare these pregnancies with those of women who also needed similar assisted reproductive techniques, of similar socioeconomic status, and cared for by a small group of 8 physicians applying consistent diagnostic and treatment approaches. STUDY DESIGN: A retrospective review of 50 consecutive pregnancies achieved by DE- IVF and 50 consecutive pregnancies achieved by standard IVF (STD-IVF) was performed. Comparisons were made for demographic and medical confounding factors and for outcome measures. RESULTS: The 2 groups were nearly identical for gravidity, parity, and multiple gestations but did vary in maternal age. Average age of patients receiving DE-IVF was 41.9(+/-5.1), whereas the STD-IVF averaged 37.7(+/-3.6) years ( P < .001). Key obstetric outcomes did not differ between the 2 groups with the exception of pregnancy-induced hypertension. In patients with DE-IVF, 26% had pregnancy-induced hypertension (PIH) develop, whereas this occurred in only 8% of the STD-IVF group ( P = .02). Examining nulliparous patients only, 37.1% of DE-IVF had PIH develop, whereas only 8% of STD-IVF group achieved that diagnosis ( P < .003). An analysis with a multiple logistic regression in nulliparous patients found odds ratios of 7.1 (95% CI, 1.4-36.7) in DE versus STD-IVF, odds ratio 4.9 (95% CI, 1.3-18.3) for multiple gestation versus singleton, and odds ratio 1.0 (95% CI, 0.9-1.1) for maternal age. CONCLUSION: Nulliparous pregnancies achieved by DE-IVF are associated with an increased risk of PIH; however, excellent outcomes can still be expected.     

Successful pregnancies after in vitro fertilization in a female previously treated for ovarian carcinoma

We report an ovarian cancer patient treated conservatively with unilateral salpingo-oophorectomy and due to infertility subjected to unstimulated in vitro fertilization. The treatments resulted in two successful pregnancies.     

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.     

Progesterone levels on the hCG day and outcomes in vitro fertilization in women with polycystic ovary syndrome

Background

The purpose of this study was to determine the incidence of premature luteinization in patients with polycystic ovary syndrome and compared the main determinants of success in in-vitro fertilization in PCOS patients with and without premature luteinization.

Methods

Retrospective analysis of 180 PCOS women of Chinese Han origin with infertility who underwent controlled ovarian hyperstimulation (COH) with an exogenous gonadotropin/GnRH antagonist protocol. Hormone levels on the hCG day and IVF outcomes were assessed.

Results

The incidence of premature luteinization was 23.3 %. Compared with PCOS patients without premature luteinization, PCOS patients with premature luteinization(PL) had a higher number of oocytes retrieved (18.20 ± 6.6 vs 15.08 ± 7.3, p = 0.037) and a higher fertilization rate (72.9 ± 1.9 vs63.1 ± 2.3, p = 0.033), but clinical pregnancy rates were no statistical significance (53.3 vs 56.0, p = 0.836). Though the implantation rate was higher in no premature luteinization patients, but the difference was not statistically significant (37.7 vs 30.3, p = 0.115).

Conclusion

The PCOS patients with premature luteinization had a higher fertilization rate and high number of oocytes retrieved, and the similar implantation rate and clinical PRs as PCOS patients without premature luteinization.     

Fetal and neonatal alloimmune thrombocytopenia in pregnancies involving in vitro fertilization: a report of four cases

OBJECTIVE: We report four cases of neonatal alloimmune thrombocytopenia (NATP) in pregnancies achieved with in vitro fertilization. STUDY DESIGN: Three cases used surrogate carriers, and the fourth a donor egg. Sera from gestational carriers were tested for platelet antibodies by flow cytometry and enzyme-linked immunosorbent assay. Platelet antigen genotyping of biologic mothers, fathers, and surrogates was performed by amplification of DNA by using polymerase chain reaction with sequence-specific primers. RESULTS: In all 4 cases, NATP resulted from an incompatibility between the fetus and gestational carrier for the platelet-specific alloantigen HPA-1a. Four infants were born severely thrombocytopenic (platelets <50,000/muL), 2 had antenatal intracranial hemorrhage, and 1 fetus expired in utero at 29 weeks. CONCLUSION: NATP can occur in the setting of assisted reproductive technology. Because of the great costs, both financial and emotional, associated with these pregnancies, we strongly recommend that all women be typed for HPA-1a before serving as a surrogate mother.     

Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization

OBJECTIVE: Exploration of the possibility that local injury of the endometrium increases the incidence of implantation. DESIGN: Prospective study. SETTING: Clinical IVF unit. PATIENT(S): A group of 134 patients, defined as good responders to hormonal stimulation, who failed to conceive during one or more cycles of IVF and embryo transfer (ET). INTERVENTION(S): The IVF treatment and ET were preceded by repeated endometrial biopsies, in a randomly selected 45 of a total of 134 patients. MAIN OUTCOME MEASURES: Outcome of IVF-ET treatments. RESULT(S): Transfer of a similar number of embryos (3.4 +/- 1.0 and 3.1 +/- 0.9 in the experimental and control patients, respectively) resulted in rates of implantation (27.7% vs. 14.2%, P =.00011), clinical pregnancy (66.7% vs. 30.3%, P =.00009), and live births per ET (48.9% vs. 22.5%, P =.016) that were more than twofold higher in the experimental group as compared to controls. CONCLUSION(S): These results suggest that IVF treatment that is preceded by endometrial biopsy doubles the chance for a take-home baby.     

Outcome of pregnancies achieved by in vitro fertilisation techniques and diagnosed as twins at the 6 week ultrasound

BACKGROUND: To bring the success rate of in vitro fertilisation (IVF) procedures to an acceptable level, multiple embryos have historically been replaced. This has resulted in an 'epidemic' of multiple births. The pendulum has now swung full circle and the number of embryos transferred is now being limited. Such high numbers of IVF twins will not be produced in the future. AIM: To review retrospectively the outcome of a series of pregnancies achieved by IVF where the 6 week ultrasound showed the presence of two sacs. METHODS: Retrospective study in a university IVF programme that produced 746 IVF pregnancies with twins at 6 weeks of gestation (1991-1999). RESULTS: The main outcome measures were perinatal mortality, pregnancy outcome, gestation at delivery and obstetrics complications reported. Interestingly, by 20 weeks gestation, 184 (24.7%) of pregnancies spontaneously reduced to a singleton, whereas 49 (6.6%) lost both twins. Of the 513 (68.8%) viable twin pregnancies (>20 weeks), 154 (20.6%) went on to term (>37 weeks), whereas 250 (33.5%) delivered between 33 and 36 weeks gestation. The perinatal mortality per 1000 births was 6.5 over 37 weeks, 8.0 for 33-36 weeks, 41.7 for 29-32 weeks and 500 for under 28 weeks.     

Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization

OBJECTIVE: To determine whether administration of methylprednisolone to high-risk women undergoing IVF/ICSI helps reduce the development of OHSS.DESIGN: Retrospective clinical controlled study.SETTING: IVF unit.PATIENT(S): One thousand ten women who underwent IVF/ICSI from January 9, 1997, to December 31, 1999. Ninety-one patients who were at high risk for OHSS were identified by using standard criteria.INTERVENTION(S): Methylprednisolone, 16 mg/d starting on day 6 of the stimulation and tapered after the first pregnancy test (day 13 after embryo transfer).MAIN OUTCOME MEASURE(S): Occurrence of OHSS.RESULT(S): A significantly lower proportion of methylprednisolone recipients than untreated participants developed OHSS (10.0% vs. 43.9%). Treatment recipients had more oocytes retrieved and more embryos fertilized than did untreated participants. Methylprednisolone treatment was equally effective in preventing OHSS in all causes of infertility and was effective independent of the number of IVF trials and pregnancy rates.CONCLUSION(S): Treatment with methylprednisolone appears to reduce the risk for OHSS. This treatment thus helps to avoid hospitalization, reduces cycle cancellations, and improves the cost-effectiveness of IVF cycles.     

Consequences of premature progesterone elevation on the outcome of in vitro fertilization: insights into a controversy

Objective: To investigate whether the consequences of premature P elevation on IVF-ET outcome are modulated by the quality of the ovarian response to controlled ovarian hyperstimulation (COH).Design: Retrospective analysis.Setting: Assisted Reproduction Unit, Clamart, France.Patient(s): One thousand twelve women undergoing 1,189 IVF-ET cycles.Intervention(s): Patients underwent COH with a time-released GnRH agonist and hMG. The ovarian response to COH was classified as strong (550 hMG ampules, peak E₂ levels > 2,500 pg/mL, and ≥10 mature oocytes; n = 340), weak (> 50 hMG ampules, peak E₂ levels ≤1,500 pg/mL, and ≤5 mature oocytes; n = 285), or intermediate (remaining cases; n = 564). The IVF-ET outcome in each group was analyzed according to whether or not plasma P levels exceeded 0.9 ng/mL.Main Outcome Measure(s): Pregnancy rates (PRs).Result(s): Clinical PRs were similar irrespective of low or high P levels in the strong (30% and 34%, respectively) and intermediate (31% and 30%, respectively) groups. However, in the weak group, P levels > 0.9 ng/mL were associated with lower PRs (3.2% and 23%, respectively).Conclusion(s): In the presence of an adequate response to COH, P levels > 0.9 ng/mL were not associated with lower PRs, indicating that good embryo quality may compensate for the adverse endometrial effects of P. Conversely, when the response to COH was weak, premature P elevation led to drastically reduced PRs.     

Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop prior to human chorionic gonadotropin.

OBJECTIVE: To study the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in in vitro fertilization cycles. METHODS: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 at Brigham and Women's Hospital were reviewed, and 65 cycles in which oocyte retrieval (ER) was performed following a drop in serum estradiol (E(2)) not associated with intentional withdrawal of gonadotropins were identified. Daily gonadotropin dose was decreased at some time in 25 of these cycles, while the remaining 40 cycles did not have a reduction in gonadotropin dose. A retrospective case-control study of the respective live birth rates and pregnancy loss rates of patients with unpredictable E(2) drops in the 65 study cycles were compared to 65 age matched controls. RESULTS: Live birth rates (32% vs. 35%, p=0.72) and pregnancy loss rates (28% vs. 30%, p=0.76) were similar for all study and control groups respectively. There were no differences in live birth and pregnancy loss rates in cycles undergoing gonadotropin dose reduction (40% vs. 44%, p=0.78 and 29% vs. 39%, p=0.70) and cycles without gonadotropin dose reduction (28% vs. 30%, p=0.81 and 27% vs. 20%, p=0.72). CONCLUSIONS: In the absence of coasting, a drop in serum estradiol levels during GnRH-agonist downregulated controlled ovarian hyperstimulation for IVF prior to hCG is not associated with a decrease in live birth rates or pregnancy loss rates.