Micronutrients in Multiple Pregnancies-The Knowns and Unknowns: A Systematic Review.

Maternal diet and nutritional status are of key importance with regard to the short- and long-term health outcomes of both the mother and the fetus. Multiple pregnancies are a special phenomenon in the context of nutrition. The presence of more than one fetus may lead to increased metabolic requirements and a faster depletion of maternal macro- and micro- nutrient reserves than in a singleton pregnancy. The aim of this systematic review was to gather available knowledge on the supply and needs of mothers with multiple pregnancies in terms of micronutrients and the epidemiology of deficiencies in that population. It was constructed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). The authors conducted a systematic literature search with the use of three databases: PubMed/MEDLINE, Scopus and Embase. The last search was run on the 18 October 2020 and identified 1379 articles. Finally, 12 articles and 1 series of publications met the inclusion criteria. Based on the retrieved studies, it may be concluded that women with multiple pregnancies might be at risk of vitamin D and iron deficiencies. With regard to other microelements, the evidence is either inconsistent, scarce or absent. Further in-depth prospective and population studies are necessary to determine if nutritional recommendations addressed to pregnant women require adjustments in cases of multiple gestations.

Luteal activity following follicular drainage of subordinate follicles for twin pregnancy prevention in bi-ovular dairy cows.

Twin pregnancy is undesirable in dairy cattle. This study examines luteal activity following ultrasound-guided puncture and drainage of the smaller pre-ovulatory follicle at timed AI in cows with a pre-ovulatory follicle in each ovary. Luteal activity was determined through Doppler ultrasonography and plasma progesterone (P4) concentrations. The effects of GnRH treatment on Day 7 post-AI on subsequent luteal activity were also assessed. Two study groups were established: a control group of 29 cows and a follicular drainage (FD) group of 28 cows. After drainage, all cows developed a corpus luteum (CL) in the drained ovary. On Day 21 post-AI, drainage-induced CL and fellow CL were similar in terms of size and vascularization. According to a GLM repeated measures analysis of variance (P < 0.001), non-treated drained cows had lower P4 concentrations on Day 21 post-AI than non-treated non-drained cows, whereas GnRH treated cows, both drained and non-drained, showed the highest P4 concentrations at this time point. Twin pregnancy was recorded in 3 of the 8 pregnant control cows, whereas no twins were observed in the FD group. Our results indicate that luteal structures following follicular drainage were functional. As for the presence of an additional CL, this could suggest a reduced risk of pregnancy loss. In addition, luteal activity was significantly increased following GnRH treatment on Day 7 post-AI in drained cows.

Follicle stimulating hormone versus clomiphene citrate in intrauterine insemination for unexplained subfertility: a randomized controlled trial.

STUDY QUESTION: Is FSH or clomiphene citrate (CC) the most effective stimulation regimen in terms of ongoing pregnancies in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria as a measure to reduce the number of multiple pregnancies? SUMMARY ANSWER: In IUI with adherence to strict cancellation criteria, ovarian stimulation with FSH is not superior to CC in terms of the cumulative ongoing pregnancy rate, and yields a similar, low multiple pregnancy rate. WHAT IS ALREADY KNOWN: FSH has been shown to result in higher pregnancy rates compared to CC, but at the cost of high multiple pregnancy rates. To reduce the risk of multiple pregnancy, new ovarian stimulation regimens have been suggested, these include strict cancellation criteria to limit the number of dominant follicles per cycle i.e. withholding insemination when more than three dominant follicles develop. With such a strategy, it is unclear whether the ovarian stimulation should be done with FSH or with CC. STUDY DESIGN, SIZE, DURATION: We performed an open-label multicenter randomized superiority controlled trial in the Netherlands (NTR 4057). PARTICIPANTS/MATERIALS, SETTING, METHODS: We randomized couples diagnosed with unexplained subfertility and scheduled for a maximum of four cycles of IUI with ovarian stimulation with 75 IU FSH or 100 mg CC. Cycles were cancelled when more then three dominant follicles developed. The primary outcome was cumulative ongoing pregnancy rate. Multiple pregnancy was a secondary outcome. We analysed the data on intention to treat basis. We calculated relative risks and absolute risk difference with 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: Between July 2013 and March 2016, we allocated 369 women to ovarian stimulation with FSH and 369 women to ovarian stimulation with CC. A total of 113 women (31%) had an ongoing pregnancy following ovarian stimulation with FSH and 97 women (26%) had an ongoing pregnancy following ovarian stimulation with CC (RR = 1.16, 95% CI: 0.93-1.47, ARD = 0.04, 95% CI: -0.02 to 0.11). Five women (1.4%) had a multiple pregnancy following ovarian stimulation with FSH and eight women (2.2%) had a multiple pregnancy following ovarian stimulation with CC (RR = 0.63, 95% CI: 0.21-1.89, ARD = -0.01, 95% CI: -0.03 to 0.01). LIMITATIONS, REASONS FOR CAUTION: We were not able to blind this study due to the nature of the interventions. We consider it unlikely that this has introduced performance bias, since pregnancy outcomes are objective outcome measures. WIDER IMPLICATIONS OF THE FINDINGS: We revealed that adherence to strict cancellation criteria is a successful solution to reduce the number of multiple pregnancies in IUI. To decide whether ovarian stimulation with FSH or with CC should be the regimen of choice, costs and patients' preferences should be taken into account. STUDY FUNDING/COMPETING INTEREST(S): This trial received funding from the Dutch Organization for Health Research and Development (ZonMw). Prof. Dr B.W.J. Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for Merck, ObsEva and Guerbet. The other authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: Nederlands Trial Register NTR4057. TRIAL REGISTRATION DATE: 1 July 2013. DATE OF FIRST PATIENT'S ENROLMENT: The first patient was randomized at 27 August 2013.

Additional small dose of prostaglandin F2α at timed artificial insemination failed to improve pregnancy risk of lactating dairy cows.

Two experiments were performed to test the hypothesis that administering PGF2α concurrent with timed artificial insemination (AI) in lactating dairy cows would enhance pregnancy per AI (P/AI). In experiment 1, lactating Holstein cows (n = 289) in one herd were enrolled after a non-pregnancy diagnosis (30-36 d after AI) to synchronize subsequent ovulation before AI. Cows were assigned randomly to receive (im) 10 mg of PGF2α concurrent with timed AI (Day 0; treatment) or no injection (control). Blood samples were collected on Days -3, 0, and 13 to determine serum concentrations of progesterone. Ovaries were scanned via transrectal ultrasonography to determine follicle diameters (Day -3), subsequent ovulation risk (Day 13), and total volume of luteal tissue (Day 13). Diagnosis of pregnancy occurred on Days 32 and 80 after AI. Ovulation risk post-AI exceeded 90% and did not differ between treatments. In addition, PGF2α treatment only numerically increased progesterone (5.7 ±â€¯0.3 vs. 6.2 ±â€¯0.3 ng/mL) or luteal tissue volume (8.9 ±â€¯0.4 vs. 9.8 ±â€¯0.5 ng/mL) on Day 13 by 8.8% (P = .206) or 10.1% (P = .134) in control and treated cows, respectively. Pregnancy per AI at Days 32 (P = .50) and 80 (P = .33) did not differ between treatments. Cows with progesterone >0.5 ng/mL at timed AI had reduced (P < .001) ovulation risk but risk was unaffected by treatment. In experiment 2, lactating dairy cows (n = 1828) in two commercial dairy herds were enrolled at time of insemination (Day 0), and assigned randomly to treatment or control as described in experiment 1. Initial (Days 32-35) and confirmed (Days 63-68) pregnancy diagnosis revealed no differences in P/AI or pregnancy loss. Pregnancy diagnosis on Days 32-35 produced percentage increases in P/AI for primiparous compared with multiparous cows (20.8%; P = .002), for first-service compared with repeat-service cows (26%; P = .001), and cows in one herd compared with the second herd (36%; P < .001). Pregnancy loss was greater (P = .001) for cows inseminated at first (10.0%) vs. later services (5.3%) but was unaffected by treatment. Cows treated with PGF2α in one herd produced more twins than control cows (11.7 vs. 3.2%), whereas no treatment difference was detected in the second herd (5.6 vs. 5.6%), respectively. We conclude that im treatment of lactating dairy cows with 10 mg of PGF2α concurrent with timed AI did not improve P/AI or embryo survival, but increased twinning in one herd.

Progesterone supplementation in the early luteal phase after artificial insemination improves conception rates in high-producing dairy cows.

This study examines the possible effects on the reproductive performance of high-producing dairy cows of progesterone (P4) given in the early luteal phase (1.55 g of P4), from Days 3 to 5 post-artificial insemination (AI) as compared with the time of pregnancy recognition, from Days 15 to 17 post-AI. Cows in their third day post-AI were alternately assigned on a weekly rotational basis to the following groups: control, no treatment (C: n = 351), P4 treatment started 15 days after AI (P4-D15: n = 261), or P4 treatment started 3 days after AI (P4-D3: n = 203). Based on odds ratios, cows in P4-D3 were 1.71 times more likely to conceive than control cows (P = 0.004), whereas cows in P4-D15 showed a 1.4-fold greater risk approaching significance of becoming pregnant compared with control cows (P = 0.06). Differences were not observed between treatments. In nonpregnant cows, the given treatment (D3 vs. D15) had no effect on subsequent return to estrus or AI interval and neither were any effects of treatment observed on early fetal loss rates. In contrast, in pregnant cows, the relative risk of twin pregnancy was 2.5 times higher for those in P4-D15 (P = 0.02) than the remaining cows. These findings indicate the efficacy of P4 supplementation after AI. However, when given at the time of pregnancy recognition rather than in the early luteal phase, this treatment increases the twin pregnancy rate.

Twin reduction by PGF2α intraluteal instillation in dairy cows.

The objective of this study was to determine whether induced luteolysis of one of the two corpora lutea in twin pregnancies would provoke spontaneous twin reduction. In Experiment 1, 12 post-partum cows with two corpora lutea in the same ovary were assigned to (three cows per group): Group I, Group II, Group III or Group IV receiving into one of the corpora lutea puncture with no treatment, 0.5 mg dinoprost, 1.5 mg dinoprost and 2.5 mg dinoprost, respectively. One of the two corpora lutea showed clear signs of luteolysis on Day 2 and was practically non-detectable on Day 7 after treatment in the three cows of the Group IV. In Experiment 2, 11 cows carrying live twins with two corpora lutea on Day 28 of gestation, eight bilateral and three unilateral, received 2.5 mg dinoprost into one of the corpora lutea. Corpus luteum reduction and embryo reduction after treatment were registered in 10 and 9 cows, respectively. In bilateral twin pregnancies, four cows suffering embryo reduction remained pregnant. In unilateral twin pregnancies, membrane detachment resulted in the death of both cotwins. In conclusion, although observations were based on few animals, there seems to be a mechanism that operates locally to transfer ovarian progesterone to the uterus, and also a quantitative relationship between the amount of progesterone secreted and support of conceptuses, resulting in death of one twin embryonic vesicle when one corpus luteum regresses.

Ovarian Stimulation, Intrauterine Insemination, Multiple Pregnancy and Major Congenital Malformations: A Systematic Review and Meta- Analysis- The ART_Rev Study.

INTRODUCTION: Multiple pregnancies are a recognized adverse effect of assisted reproductive technologies; nevertheless, there is no consensus on the incremental risk associated with the ovarian stimulation (OS) used alone and intrauterine insemination (IUI). The relationship between OS and IUI and the risk of major congenital malformations (MCM) is unclear. OBJECTIVE: To summarise the literature and evaluate the risk of multiple pregnancy and MCM associated with OS used alone and IUI used with or without OS compared to natural conception (spontaneously conceived infants without any type of fertility treatments). METHODS: We carried out a systematic review to identify published papers between 1966 and 2014 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We included observational studies and randomized clinical trials related to the risk of multiple pregnancies and MCM conceived following OS alone or IUI compared to natural conception (spontaneously conceived infants without any fertility treatments). The quality of the included studies was evaluated using The Cochrane Collaboration's tool for assessing risk of bias for RCTs and the Newcastle-Ottawa Scale for observational studies. RESULTS: There were 63 studies included in this review. Our systematic review suggests that the use of any OS alone was associated with an increased risk of multiple pregnancy compared to natural conception (pooled RR 8.80, 95% CI 5.09- 15.20; p= 0.000; 9 studies). Similar increases in the risk of multiple pregnancies were observed following clomiphene citrate used without assisted reproductive technologies. Compared to natural conception, the use of IUI with or without OS was associated with an increased risk of multiple pregnancy (pooled RR 9.73, 95% CI 7.52 -12.60; p= 0.000; 6 studies). Compared to natural conception, the use of any OS alone was associated with an increased risk of any MCM (RR pooled 1.18, 95%CI 1.03-1.36; 11 studies), major musculoskeletal malformations (pooled RR 1.48, 95%CI 1.21-1.81; 7 studies), and malformations of the nervous system (pooled RR 1.73, 95%CI 1.15-2.61; 6 studies). Compared to natural conception, the use of IUI was associated with an increased risk of any MCM (pooled RR 1.23, 95%CI 1.10-1.37; 10 studies), major urogenital (pooled RR 1.52, 95%CI 1.04-2.22; 7 studies), and musculoskeletal malformations (pooled RR 1.54, 95%CI 1.20-1.98; 7 studies). The overall quality of the included studies was acceptable. CONCLUSIONS: The increased risk of multiple pregnancy and certain types of MCM associated with the use of less invasive fertility treatments, such as OS and IUI, found in this review, highlights the importance of the practice framing. Heterogeneity in OS protocols, the combination with other fertility agents, the limited number of studies and the methodological quality differences reduce our ability to draw conclusions on specific treatment. More observational studies, assessing the risk of multiple pregnancy or MCM, as a primary outcome, using standardized methodologies, in larger and better clinically defined populations are needed.

Number of Intermediate Follicles. An Independent Risk Factor of Multiple Pregnancies in Intrauterine Insemination Cycles with Recombinant Follicle-Stimulating Hormone.

OBJECTIVE: To identify risk factors for multiple pregnancies in intrauterine insemination (IUI) cycles with recombinant follicle-stimulating hormone (r-FSH). STUDY DESIGN: A retrospective study including 205 IUI cycles with r-FSH which led to clinical pregnancies was conducted. A total of 145, singleton pregnancies and 60 multiple pregnancies were compared according to clinical characteristics and parameters of ovarian stimulation and IUI procedure. The relationships between size and number of follicles and serum estradiol (E2) levels and the risk of multiple pregnancies were investigated using multiple logistic regression analyses. RESULTS: The means of infertility length, serum E2 levels, the number of follicles 10 mm, 12 mm, and ≥ 16 mm, and the number of intermediate follicles (from 12 to ≤ 15 mm) at the day of ovulation triggering were significantly higher in the multiple pregnancy group as compared to in the singleton pregnancy group (p < 0.05). We first demonstrated that high E2 levels (≥ 1,000 pg/nL) and the number of intermediate follicles represent 2 independent and significant risk factors for multiple gestation in IUI cycles that used ovarian stimulation by r-FSH (p = 0.002 and p = 0.007, respectively). CONCLUSION: This study shows that high E2 levels and the number of intermediate follicles, independently of large follicles, can predict an increased risk of multiple pregnancy in r-FSH IUI cycles.

The addition of gonadotrophin releasing hormone agonist to routine luteal phase support in intracytoplasmic sperm injection and embryo transfer cycles: a randomized clinical trial.

OBJECTIVES: To determine the effects of addition of different dosages of gonadotrophin releasing hormone agonist (GnRH-a) to routine luteal phase support (LPS) on implantation and pregnancy rates. STUDY DESIGN: Three hundred infertile couples who were treated by intracytoplasmic sperm injection and embryo transfer (ICSI-ET) following controlled ovarian stimulation (COS) with long luteal GnRH agonist protocol were enrolled. All women received 600 mg/day vaginal micronized progesterone plus 4 mg 17ß estradiol for LPS starting from the day of oocyte retrieval. Patients (n=300) were randomized into three treatment groups. Group A (n=100) received leuprolide acetate 1 mg s.c. injection 3 days after ET in addition to routine LPS. Group B (n=100) received two sequential doses of leuprolide acetate 1 mg s.c. injections 3 and 6 days after ET in addition to routine LPS. Control group (n=100) received only the routine LPS. RESULTS: A total of 279 patients completed the study. The groups were comparable in terms of baseline demographic parameters including age, duration of infertility and day 3 levels of FSH and estradiol. The cycle parameters of the groups were also comparable regarding the E2 level on day of hCG, number of retrieved oocytes, number of day 3 embryos, number of embryos transferred, and endometrial thickness on both days of OPU and ET. The implantation rates were similar in between the Groups A, B, and control group (20.7% and 25.8% vs. 13.3%, respectively; P=.099). The clinical pregnancy rates and miscarriage rates were similar in between the groups. The ongoing pregnancy rates were 27.4% in control group, 36% in Group A and 42.9% in Group B (P=.093). The OHSS rates were comparable in between the groups. The multiple pregnancy rates were significantly higher in Groups A and B than in control group (12% and 17.9% vs. 4.2%, respectively; P=.014). CONCLUSIONS: The implantation, clinical pregnancy and ongoing pregnancy and multiple pregnancy rates seem to be increased with the addition of GnRH-a to routine luteal phase support.

Positive effects of melatonin treatment on the reproductive performance of young border leicester rams mated to merino ewes in spring: preliminary observations.

Poor reproductive performance of Merino ewe flocks when mated to Border Leicester rams during spring may be due to seasonality of the Border Leicester breed. Two approaches were taken to test this assumption. Six young (12 months old) or six mixed-age (12, 24 and ≥36 months old) Border Leicester rams were either treated or not treated with melatonin implants (2 × 2 design) 6 weeks before the four groups of rams were each put with approximately 300 Merino ewes for an 8-week mating period. Implants were inserted in early September (experiment 1). The second approach was to yard or not yard ewes and mixed-age rams on several occasions during the first 3 weeks of the mating period (experiment 2). Pregnancy rate and twinning percentage were assessed by ultrasonography. In experiment 1, melatonin treatment in young rams increased (p < 0.001) pregnancy rate from 5.0% to 92.6%, but mixed-age rams did not respond (90.7% vs 89.5% for melatonin and non-melatonin treatments, respectively). Twinning rate was similar (p > 0.05) for ewes mated to either melatonin or non-melatonin-treated young rams (36.8% vs 40.0%, respectively), whereas melatonin significantly improved (p < 0.05) twinning rate in those ewes mated to mixed-age rams (49.1% vs 36.1%). After 6 weeks of melatonin treatment, scrotal circumference was greater (p < 0.05) in both young and mixed-aged rams than in untreated counterparts. In experiment 2, yarding of ewes and rams overnight on several occasions early in the mating period reduced (p < 0.001) pregnancy rate compared with non-yarded counterparts (89.5% vs 65.5%). Twinning rate was not affected (37.7% vs 36.1%, respectively). In summary, melatonin treatment of Border Leicester rams significantly improved flock reproductive performance in spring due to improved pregnancy rates with young rams and improved litter size with mixed-age rams.

Use of progestogens in pregnant and infertile patients.

Progesterone is an essential hormone in the occurence and maintenance of pregnancy. Natural or synthetic progestogens are commonly used in pregnant patients or patients undergoing infertility treatments for various indications. Most frequently put indications for the use of progestogens in these patient populations are the prevention of spontaneous preterm birth, the prevention of pregnancy loss in pregnancies with an unexplained recurrent pregnancy loss and in patients with threatened abortion. It is also used in pregnant women undergoing nonobstetric surgery, for infertility or recurrent pregnancy loss that is thought to be due to luteal phase defect or as a luteal support in stimulated IVF cycles. We aimed to review the current evidence for the use of progestogens in each of these settings.

Effect of prolonged in vivo administration of progesterone in pregnancy on myometrial gene expression, peripheral blood leukocyte activation, and circulating steroid hormone levels.

OBJECTIVE: We aimed to investigate the effects of progesterone on gene expression and function of both myometrium and circulating leukocytes. METHODS: We recruited women participating in a randomized clinical trial of progesterone to prevent preterm delivery. These participants had a twin pregnancy and were managed in 1 of 2 tertiary referral centers. Participants were treated with progesterone (90 mg vaginally) or placebo from 24 to 34 weeks of pregnancy. The outcome measures were myometrial and leukocyte gene expression and expression of cell surface markers in circulating leukocytes, all quantified ex vivo. RESULTS: Prolonged in vivo administration of progesterone inhibited myometrial expression of connexins 26 and 43, endothelial nitric acid synthase (eNOS), and the prostaglandin receptor EP2 ex vivo. Administration of progesterone also increased numbers of circulating neutrophils while decreasing lymphocyte proportions and decreasing neutrophil CD11b expression. CONCLUSION: The observed effects of prolonged in vivo administration of progesterone will minimize the ability of the uterus to contract as a synctium and the ability of peripheral blood leukocytes to migrate into the myometrium during parturition. We suggest that these are putative mechanisms by which progesterone might prevent preterm birth in women at high risk.

The therapeutic management of a twin pregnancy complicated by the presence of cervical cancer, following laparoscopic staging and chemotherapy, with an emphasis on cisplatin concentrations in the fetomaternal compartments amnion fluid, umbilical cord, and maternal serum.

OBJECTIVE: To evaluate the feasibility, toxicity, and pharmacokinetics in the maternal and fetal compartments during chemotherapy in a pregnant patient with cervical cancer. DESIGN: Case report. SETTING: University Hospital. PATIENT: A 35-year-old woman was diagnosed with an adenocarcinoma FIGO stage IB1 of the cervix uteri at 14 weeks' gestation with twin pregnancy. INTERVENTION(S): A laparoscopic transperitoneal pelvic lymphadenectomy was performed at 15 weeks' gestation There was no evidence of lymph node metastases (0/19). The patient decided to continue her pregnancy. Three cycles of neoadjuvant chemotherapy consisting of cisplatin during the second and third trimester were given and well tolerated. Amniocentesis was performed at the time of the second cisplatin cycle. MAIN OUTCOME MEASURE(S) AND RESULT(S): The concentration in the amniotic fluid samples reached 10% of the maternal blood levels at this time. At 32 weeks' gestation, a Caesarean section followed by radical hysterectomy was performed. The twins developed normally and displayed no chemotherapically related side effects. At the time of delivery, the corresponding concentration in the amniotic fluid was approximately one-third of the umbilical cord levels. CONCLUSION(S): To our knowledge, this is the first report quantifying the amount of transplacental transport of cisplatin during pregnancy in vivo. One-tenth of the maternal serum concentration was detected in the amniotic fluid; the concentration of cisplatin in the umbilical cord was three times higher than in the amniotic fluid.

The efficacy of different hCG dose rates and the effect of hCG treatment on ovarian activity: ovulation, multiple ovulation, pregnancy, multiple pregnancy, synchrony of multiple ovulation; in the mare.

Despite the widespread use of hCG to advance ovulation in the mare there is little information on efficacy of dose rates and any contraindications of its use. This study aims to investigate the effect of dose of hCG on ovulation within 48h and the effect of hCG on: ovulation, multiple ovulation (MO), pregnancy, multiple pregnancy (MP) rates and synchrony of MO; additionally whether any seasonal effect is evident. Sequential ultrasonic scanning was used to monitor the occurrence of ovulation, within 48h of treatment, in 1291 Thoroughbred mares treated with either 750iu hCG or 1500iu hCG s.c. Ovulation rate, type (single ovulations (SO), MO, synchronous, asynchronous) and subsequent pregnancy were then monitored in 1239 Thoroughbred mares on a commercial stud over 3 years, 536 of which were treated with 750iu hCG at mating, all mares were also allocated into groups according to month of mating. No significant difference existed between the two dose levels of hCG and no significant difference existed between treated and untreated mares in overall ovulations (1.32 and 1.28 respectively), MO (31.7% and 27.7%), pregnancy (65.1% and 65.6%) or MP rates (10.8% and 11.8%). There was no significant association between month of year and pregnancy or MP rates for either treated or control mares, nor for MO for untreated mares. A significant (p<0.05) association was evident between month and MO in treated mares, MO being lowest in April (22.3%). 95.9% of treated mares multiple ovulated within 48h compared with 90.7% controls, a near significant difference. In conclusion this study demonstrates that: (i) hCG dose of 750iu s.c. is just as effective in inducing ovulation within 48h as 1500iu, (ii) 750iu hCG has no significant effect on ovulation, MO, pregnancy or MP rates; (iii) a significant (p<0.05) association exists between season and MO in hCG treated mares; (iv) a tighter synchrony (ovulation within 48h) of MO is evident in hCG treated compared with control mares (p=0.052).

A prospective comparison of vasopressor requirement and hemodynamic changes during spinal anesthesia for cesarean delivery in patients with multiple gestation versus singleton pregnancy.

BACKGROUND: It is commonly taught that patients with multiple gestation pregnancy are prone to more severe hypotension during spinal and epidural anesthesia compared to those with singleton pregnancy. However, few quantitative data are available to support this claim. In this study, we prospectively compared vasopressor requirement and hemodynamic changes in patients with multiple gestation versus singleton pregnancy during spinal anesthesia for elective cesarean delivery. METHODS: Forty parturients with multiple gestation and 60 singleton controls who had identical anesthetic management during spinal anesthesia for elective cesarean delivery were enrolled. After IV prehydration, patients received intrathecal bupivacaine-fentanyl and were tilted to the left. A metaraminol infusion was titrated with the target of maintaining systolic blood pressure at 90%-100% of baseline. Vasopressor dose, minimum and maximum values for systolic blood pressure and the incidences of hypotension, hypertension, and nausea/vomiting were compared. RESULTS: All outcome variables were similar between groups. The total dose of metaraminol required until uterine incision was similar in multiple gestation pregnancy (median 2.9 [interquartile range 2.0-3.7] mg) when compared with singleton pregnancy (median 3.1 [interquartile range 2.3-3.9] mg, P = 0.25; median difference 0.30 mg, 95% confidence interval of difference -0.20 to 0.90 mg). Neonatal outcome was similar between groups. CONCLUSION: Patients with multiple gestation pregnancy do not exhibit greater hemodynamic instability during spinal anesthesia for cesarean delivery compared to those with singleton pregnancy.

Increase of multiple pregnancies caused by ovulation induction with gonadotropin in combination with metformin in infertile women with polycystic ovary syndrome.

Metformin appears to be an effective medicine to induce ovulation in women with polycystic ovary syndrome and insulin resistance. After the introduction of metformin treatment for such cases, the use of gonadotropin in combination with metformin significantly increased the incidence of multiple pregnancies.

Mifepristone-induced abortion in one horn and a growing fetus in another horn in a patient with a twin pregnancy in a bicornuate uterus.

OBJECTIVE: To report a case of mifepristone-induced abortion in only one horn but a growing fetus in another horn for a twin pregnancy in a bicornuate uterus. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taiwan. PATIENT(S): A 31-year-old woman who conceived spontaneously presented with 37 days' gestation. INTERVENTION(S): Mifepristone 600 mg orally followed by misoprostol 400 mug orally 2 days later. MAIN OUTCOME MEASURE(S): Termination of pregnancy. RESULT(S): Induced abortion in only one horn but a growing fetus in another horn for a twin pregnancy in the bicornuate uterus detected by ultrasound. Surgical abortion with vacuum curettage was performed, and menstruation resumed 1 month later. CONCLUSION(S): As medical abortion with mifepristone and misoprostol becomes more prevalent, more studies are necessary to establish the dosage and regimens for multiple pregnancies associated with uterine anomalies.

Is twin pregnancy necessarily an adverse outcome of assisted reproductive technologies?

It has recently been suggested that the measure of success of assisted reproductive technologies (ART) should be the birth of a singleton baby, whereas a twin pregnancy should be considered as a complication. Although the maternal and neonatal complications in twin pregnancies are significantly higher than those in singleton pregnancies, the classification of a twin pregnancy as a complication of ART is in our opinion debatable. Most twin pregnancies result in the birth of two healthy babies, with little or no complication for the mother, and only few twin pregnancies results in serious morbidity of the mother and of one or both of the children. The crux of our arguments is that one should consider those cases as poor outcomes and not a twin pregnancy per se.