Efficacy of using electrosurgical bipolar vessel sealing during vaginal hysterectomy in patients with different degrees of operative difficulty: A randomised controlled trial

Objective

To assess the efficacy of electrosurgical bipolar vessel sealing using the LigaSure^® system during vaginal hysterectomy in comparison with conventional suture ligation method.

Study design

103 patients undergoing vaginal hysterectomy for benign conditions were randomised to either LigaSure^® or Suture groups. Each group was divided into two subgroups according to the degree of surgical difficulty.

Results

Participants in the LigaSure^® had shorter procedure time (52.5 min vs. 90 min; p < 0.001) and less blood loss (230 ml vs. 360 ml; p < 0.001). Complication rates were not statistically different between the two groups. The advantage of the LigaSure^® system in reducing the operative blood loss was more pronounced in the more difficult procedures.

Conclusion

The LigaSure^® system reduces the operating time (by reducing pedicle-securing time) and blood loss without increasing the post-operative complication rates of vaginal hysterectomy. This beneficial effect was found to be more pronounced in difficult procedures.     

Surgical treatment of ectopic pregnancy by single port access with SILS® system: preliminary study

Aim

To evaluate feasibility of surgical treatment for ectopic pregnancy with single laparoscopic access with SILS^® system.

Patients and methods

We conducted an open study from 1/7/2009 to 1/12/2010 in a single gynaecologic department. All procedures were performed by three operators. Procedures evaluated were corneal resection, salpingotomy, salpingectomy. Feasibility, per- and postoperative data were reported.

Results

We performed completely 31 over 32 (97%) surgical procedures with SILS^® system (27 salpingectomies and five salpingotomies). In one case, conversion to conventional laparoscopy was required. No intra- or postoperative complications were reported.

Conclusion

Laparoscopic surgery for ectopic pregnancy by single access seems feasible with SILS^® system. Further study including larger number of patients and operators were necessary to confirm risks and advantages of this technique.     

Hysteroscopic hydrosalpinx occlusion with Essure device in IVF patients when salpingectomy or laparoscopy is contraindicated

Objective

To evaluate, in patients with hydrosalpinges, the effect on in vitro fertilization (IVF) outcome of the insertion by hysteroscopy of an intratubal blocking device, in cases where laparoscopic salpingectomy or laparoscopy was contraindicated.

Study design

A prospective interventional case series study was conducted in fifteen women with unilateral (N = 6) or bilateral hydrosalpinges (N = 9) submitted for IVF. In all of them, laparoscopic salpingectomy was contraindicated. Hysteroscopic insertion of the Essure intratubal device in a consultation room setting was performed. IVF results were compared with those of women where hydrosalpinx was treated by laparoscopic salpingectomy (48 women, 76 cycles).

Results

There were no complications during or immediately after the procedure in any of the patients. There were four pregnancies from 16 embryo-transfers with own oocytes, one spontaneous pregnancy after unilateral Essure insertion, and one pregnancy after oocyte donation. In one case the hydrosalpinx grew and pelvic inflammatory disease developed 6 months after the insertion, requiring bilateral adnexectomy. Although not of statistical significance, IVF pregnancy rates were somewhat lower than in the laparoscopic salpingectomy group, which was attributed to the lower ovarian reserve before Essure insertion.

Conclusion

The hysteroscopic insertion of the Essure intratubal device prior to IVF is a reasonable option in cases where laparoscopic salpingectomy is contraindicated. Larger series are required to assess pregnancy outcome.     

Evaluación del tratamiento médico del embarazo ectópico con metotrexato

Objectives

To evaluate the efficacy of medical treatment with methotrexate in ectopic pregnancy.

Material and methods

We performed a prospective observational study of the use and effectiveness of medical treatment with methotrexate in patients diagnosed with ectopic pregnancy in the Ciudad Real University General Hospital from 2008 to 2009. A single intramuscular dose was administered in patients who met the inclusion criteria. Medical treatment was considered to have failed when surgery was required. We analyzed the economic costs of medical and surgical treatment.

Results

We diagnosed 63 cases of ectopic pregnancy. Forty patients (63.5%) were treated with methotrexate, and 23 women (36.5%) who did not meet the criteria for inclusion in the protocol for medical treatment were treated surgically (laparoscopic salpingectomy). Among patients who received methotrexate, 30 (82.5%) required only one dose and 10 (17.5%) required two doses. Methotrexate treatment was successful in 30 patients (75%) and failed in 10 (25%), who underwent a laparoscopic salpingectomy. The cost per case of medical treatment was 580 €, which was less than the cost of laparoscopic surgical treatment (3,465.8 €).

Conclusions

Methotrexate treatment of ectopic pregnancy in selected patients is as effective as the standard treatment with laparoscopy with less cost and with high acceptance by patients.     

A Longitudinal study of body composition and basal metabolic rate during pregnancy in a black population of Kinshasa, Democratic Republic of Congo (RDC)

Objective

A longitudinal study of body composition and basal metabolic rate during pregnancy in a black population of Kinshasa.

Materials and methods

Body composition and basal metabolic rate were determined by bioimpedance, and energy intake was evaluated using the 24 h recall method at 20, 34 and > 37 weeks of gestation in 76 black, Congolese women. The subjects had to be healthy, and to deliver term, singleton infants after a normal pregnancy.

Results

At 20 weeks of pregnancy, the 76 women, aged 28.5 ± 6.4 years, had a body weight of 61.1 ± 7.7 kg, a body mass index of 23.0 ± 3.8 kg/m², a fat mass of 36.6 ± 6.8% and a basal metabolic rate of 1399 ± 84 kcal/24 h. Subsequently, increases in body weight (+6.5 kg), fat-free mass (+ 5.1 kg), body water (+4.4 l) and basal metabolic rate (+297 kcal/24 h) (P < 0.0001) were observed. The increase in fat mass (+1.4 kg) was less pronounced. Energy intake was stable.

Conclusion

Changes in body composition during pregnancy in Congolese black women are comparable to those reported in other populations. Pre- and per-gravidic fat mass is higher in congelese women than in Caucasian women.     

Erythropoietin and erythropoietin receptor expression in normal and disturbed pregnancy

Objective

Erythropoietin (Epo) is known to regulate the number of circulating erythrocytes. Epo receptor (Epo-R) expression is limited to few organs including the uterus. We investigated differences in Epo and Epo-R expression in normal and disturbed first trimester human pregnancy.

Study design

Placental tissue was obtained from normal human pregnancy, abortion and hydatidiform mole during the first trimester of pregnancy. Epo and Epo-R expression was investigated by Immunohistochemistry and real time PCR (TaqMan^®). The intensity and distribution patterns of Epo and Epo-R expression were evaluated by using a semi-quantitative method (immunoreactive score) as previously described.

Results

Epo-R expression was upregulated in the villous trophoblast (VT) of abortive tissue (p = 0.002) as compared to normal pregnancy. This was further confirmed on mRNA level. With regard to mole pregnancy, Epo-R expression was also significantly increased in the VT (p < 0.001). In extravillous trophoblasts (EVT), only Epo, not Epo-R expression was significantly increased in abortive tissue (p = 0.006) as well as in hydatidiform mole (p = 0.041) in comparison to normal pregnancy. Identification of EVT as Epo-and Epo-R-positive cells was obtained by double immunofluorescence with CK7 and Epo/ Epo-R double staining. Both mole pregnancy and abortion were accompanied by an upregulation of Epo (p = 0.041; p = 0.018) and Epo-R expression (p = 0.007; p = 0.015) in decidual tissue as compared to normal pregnancy.

Conclusion

Within our study we were able to demonstrate increased expression of Epo and Epo-R in abortive tissue and hydatidiform mole. Whether upregulation of Epo and Epo-R is secondary to placental hypoxia as part of the abortion process or a risk factor of its own, needs to be further investigated.     

Obstetric and neonatal outcome after surgical treatment of cervical dysplasia

Objectives

Conization is the gold standard today for the management of severe cervical dysplasia. However, with the increasing delay until first pregnancy, obstetric follow-up of patients with a history of conization is a growing concern.

Study design

Retrospective case–control study using data from the electronic database of a university hospital. We compared the obstetric and neonatal outcome of 106 pregnancies delivered after conization with the outcome of 212 pregnancies of patients with no history of conization.

Results

A significant reduction in the mean gestational age at delivery (38.23 ± 2.51 weeks vs. 39.15 ± 1.56 weeks) was observed, together with a higher rate of premature rupture of the membrane (9.4% vs. 1.9%), premature onset of labor (9.4% vs. 2.4%), premature delivery (17% vs. 3.8%) and neonatal hospitalization (17.9% vs. 6.6%) in the group of patients with history of conization. Children born to women who had surgery had a significantly lower birth weight (3146.9 ± 611 g vs. 3347.3 ± 502 g) and size (49.1 ± 2.6 cm vs. 50.0 cm ± 2.2 cm) than those of the control group. Furthermore, these children were more frequently admitted in the neonatal intensive care unit (22.6% vs. 10.4%, p = 0.004).

Conclusions

Conization is an important risk factor for premature birth and women with a history of conization require cautious obstetric management during pregnancy. Anti-HPV vaccination and proactive surveillance of low-grade or moderate dysplasia, instead of immediate surgery, should be encouraged in young patients.     

Pregnancy outcomes following pulsatile GnRH treatment: results of a large multicenter retrospective study

Objectives

The aim of the present study was to evaluate the efficacy of pulsatile GnRH treatment in a large French cohort of patients with hypogonadotropic hypogonadism.

Methods

A retrospective study involving all women treated with pulsatile GnRH, over a 3-year period, in 24 French centers. Pregnancy rate and pregnancy outcome were the criteria for evaluation.

Results

The study included 248 women who received a total of 829 treatment cycles. The treatment routes of administration were subcutaneous (56.1% of the patients), intravenous (31.1%), or both (12.7%). The pregnancy rate per treatment cycle was 25%, while the mean number of cycles needed to obtain a pregnancy was 2.8 ± 1.7. The miscarriage rate was 8.2% and the multiple pregnancy rates 8.8%. The mean delivery term was 38.4 ± 2.4 weeks and the mean birth weight was 3009 ± 561 g. No severe ovarian hyperstimulation was recorded. Ovarian cysts occurred in 2.3% of the treatment cycles, local allergies in 1.7%.

Conclusion

Our study has shown that pulsatile GnRH treatment was well tolerated, without severe hyperstimulation. It induced a good pregnancy rate with favorable pregnancy outcomes.     

First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia

Objective

To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive.

Study design

A retrospective case–control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11–14 weeks and stored at −70 °C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls.

Results

Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p < 0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 13.5 pg/mL, p < 0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p < 0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p < 0.001, p < 0.001 and p < 0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia.

Conclusions

Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia.     

An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing

Objective

The objective of this multicentre, non-controlled, open-label study is the evaluation of the bleeding patterns during the use of a vaginal combined contraceptive, its safety in relation to occurrence of adverse effects, its efficacy as a contraceptive method and user compliance.

Study design

Healthy female volunteers (N = 165), asking for contraception, were enrolled to participate in the study. Each subject was given seven vaginal rings, releasing an average amount of 120 μg etonogestrel (ENG) and 15 μg ethinylestradiol (EE) per day. Study period was 7 cycles. A total of 878 cycles was valid for statistical analysis. The primary parameter, (breakthrough bleeding and/or spotting), was recorded for each cycle. The subjects were asked to report any adverse effect experienced during the treatment period, general physical and gynaecological examinations were performed and haematological blood tests were taken.

Results

Breakthrough bleeding/spotting occurred in 5.01% cycles (44 out of 878 cycles, of whom 37 were breakthrough spotting only). Absence of withdrawal bleeding during the ring-free period was reported in 1.94% cycles (17 out of 878). Forty-one subjects (24.8%) reported 66 events that were potentially drug-related. The most frequently drug-related events were weight increase (10 cases), headache (9 cases), nausea (4 cases). No pregnancy was reported during the study period. Haematology and chemical chemistry tests showed no clinically significant abnormality.

Conclusions

In the present study, NuvaRing^® has shown to be a valid contraceptive method to ensure optimal cycle control with low incidence of irregular bleeding and altered withdrawal bleeding. The low incidence of gastrointestinal side effects (nausea, vomiting) may be related the low hormonal dose and to the vaginal delivery of hormones which avoids the gastrointestinal tract.     

Adoptive transfer of CD4+CD25+ regulatory T cells for prevention and treatment of spontaneous abortion

Objectives

The purpose of this study was to examine whether adoptive transfer with in vitro expanded CD4⁺CD25⁺ regulatory T cells (Tregs) could prevent immune response-mediated spontaneous abortion in mice.

Study design

Female CBA/J mice were mated with male Balb/c as the control with normal pregnancy or with DBA/2J mice as a model of spontaneous abortion. The CBA/J mice mated with DBA/2J were treated intravenously with freshly isolated or in vitro expanded Tregs on day 1 or 4 of pregnancy, respectively. The numbers of surviving and reabsorbed fetuses in the different groups of mice were counted on day 14 of pregnancy, and the concentrations of cytokines in individual sera and the supernatants of cultured Tregs were measured by ELISA.

Results

Adoptive transfer with freshly isolated Tregs only slightly reduced the fetal resorption rate, which was not significantly different from that of the mice without Treg treatment, regardless of treatment at early stage and implementation of pregnancy. In contrast, adoptive transfer with in vitro expanded Tregs significantly reduced the fetal resorption rates, particularly for treatment at early stage of pregnancy (P < 0.05). Furthermore, adoptive transfer with in vitro expanded Tregs at early stage of pregnancy significantly increased the levels of serum IL-10, TGF-β1, and the ratios of IL-10 to IFN-γ.

Conclusions

Our data clearly indicated that adoptive transfer with in vitro expanded Tregs at early stage of pregnancy protected fetuses from spontaneous abortion by re-establishing immune tolerance in mice.     

Weight retention from early pregnancy to three years postpartum: a study in Iranian women

Objectives

to examine weight retention from early pregnancy to three years postpartum in Iranian women.

Design

a prospective cohort study.

Setting

12 health centres selected at random in urban and rural areas in Guilan.

Participants

1315 pregnant women (705 in urban areas and 610 in rural areas) who regularly attended health centres for antenatal care and growth monitoring of their babies.

Measurements

details of weight, height, pregnancy weight gain, body weight at one to three years postpartum, mother's age, parity, duration of any breast feeding, education and employment status of women who carried singleton fetuses and delivered at term were collected at the first antenatal visit. The women were categorised based on their pre-pregnancy body mass index, weight retention at one to three years postpartum, employment status and educational levels.

Findings

women who gained more weight than recommended during pregnancy tended to be heavier at three years postpartum than women who gained weight within the recommended ranges during pregnancy (7.0±5.3 versus 4.8±6.7 kg; p<0.0001). Less-educated women were at greater risk for inadequate pregnancy weight gain than other educational groups, and they had less weight retention at three years postpartum than other educational groups. Also, weight retention for primiparous women was higher than that for multiparous women (5.4±6.6 versus 3.8±6.3 kg; p<0.0001). The results of logistic regression analysis revealed that only total pregnancy weight gain was independently related to major weight retention (?4 kg) at three years postpartum (odds ratio 1.34, 95% confidence intervals 1.03–1.74; p=0.02).

Conclusion

a high body mass index before pregnancy is not associated with increased risk of retaining more weight after pregnancy. On the other hand, total pregnancy weight gain was the most important determinant of weight retention at three years postpartum in this population of Iranian women.     

Does 45,X/46,XX mosaicism with 6–28% of aneuploidy affect the outcomes of IVF or ICSI?

Objective

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI.

Study design

Forty-six women with a 45,X/46,XX karyotype with 6–28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype.

Results

No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p = 0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p = 0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p = 0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p = 0.51).

Conclusion

45,X/46,XX mosaicism with 6–28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies.     

Patient goals after incontinence procedures: does the single-incision sling satisfy them?

Objective

This study was undertaken to describe short-term postoperative achievement of subjective preoperative goals for single-incision MiniArc slings, in comparison with tension-free vaginal tape (TVT).

Method

Patients submitted to mid-urethral sling (TVT and MiniArc) procedures for stress urinary incontinence (SUI) in two centers were included in this prospective study. Before surgery, the patients completed a preoperative open-ended questionnaire, in which they described their personal outcomes goals for SUI surgery and the degree of severity of their symptoms. At the first postoperative check, they were asked to assess the degree to which their goals had been met and the degree of postoperative incontinence symptoms; their grade of satisfaction was evaluated with IIQ-7, UDI-6 and a 0–10 visual analog scale.

Results

One hundred and eight patients (TVT n = 51, MiniArc n = 57) were included in this study. Incontinence symptom relief and improvement of quality of life were the most commonly described preoperative goals. Six to eight weeks after surgery, 47 patients (92.1%) after TVT and 53 (92.9%) women after single-incision slings were objectively cured (P = 1). After surgery, more than 90% of the patients in both groups achieved their preoperative goals. Symptom scores improved significantly and were comparable in both groups.

Conclusion

Our results show that self-reported achievement of preoperative goals of patients submitted to single-incision slings are comparable at the first follow-up with patients who have undergone the classic mid-urethral sling.     

Laparoscopic uterine nerve ablation versus vaginal uterosacral ligament resection in postmenopausal women with intractable midline chronic pelvic pain: a randomized study

Objective

To assess and compare the laparoscopic uterine nerve ablation (LUNA) and the vaginal uterosacral ligament resection (VUSR) in postmenopausal women with chronic pelvic pain (CPP).

Study design

Eighty postmenopausal women with intractable and severe midline CPP were randomized to undergo LUNA or VUSR. Costs of two surgical procedures were assesses. Cure rate, severity of CPP, and deep dyspareunia were also evaluated after 6 and 12 months from surgery.

Results

The mean cost of LUNA resulted significantly higher in comparison with VURS (2078 ± 637 versus 1497 ± 297, P < 0.001). The cure rate was not significantly different between the two groups at 6 (33/40, 82.5% versus 35/40, 87.5% for groups A and B, respectively; P = 0.530; RR 0.94, 95% CI 0.78–1.13), and 12 months (27/36, 75.0% versus 28/38, 73.7%, for groups A and B, respectively; P = 0.901; RR 0.90, 95% CI 0.78–1.33) of follow-up. At same times, a significant (P < 0.01) decrease in severity of CPP and deep dyspareunia was observed in both groups with no difference between them.

Conclusions

Both LUNA and VUSR are equally effective surgical treatments in postmenopausal women with central CPP but VUNR is significantly cheaper than LUNA.     

Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Objectives

Viruses and tumour cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16^INK4a molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type.

Study design

Cervical biopsies (N = 74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n = 31), CIN2–3 (n = 19), and invasive cancer (n = 14) were evaluated alongside 10 normal cervical specimens.

Results

HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR = 0.12, 95%CI: 0.0163–0.7899; p = 0.04). HLA-E expression increased with the progression of the lesion (χ²-test for trend = 4.01; p = 0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR = 11.25, 95%CI: 2.324–54.465; p = 0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16^INK4a presented a good concordance (Kappa: 0.67).

Conclusions

HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection.     

Clinical estimation of fetal weight and the Hawthorne effect

Objective

The Hawthorne effect refers to improvement in performance solely due to the subject's knowledge that he or she is being studied. We sought to determine if an obstetrician's clinical estimation of fetal weight (EFW) is influenced by the Hawthorne effect seen in some clinical trials.

Study design

We compared obstetricians’ clinical EFW's obtained during a study period to those obtained prior to the study period in one institution. We included any patient presenting at ≥37 weeks gestation. We excluded multiple pregnancies and patients with a recent sonographic EFW.

Results

There was no difference in regards to the proportion of EFW's within 10% of the birthweight (67.9% vs. 68.5%, p = .91), the mean absolute difference of EFW-birthweight (282 ± 227 g vs. 285 ± 232 g, p = .88), or the mean absolute percent error (8.5 ± 7.4% vs. 8.6 ± 7.2%, p = .96). We also could not find any Hawthorne effect when we excluded resident physicians’ EFW's and when we analyzed the subgroup of newborns with a birth weight ≥4000 g.

Conclusion

An obstetrician's knowledge that he or she is being studied is unlikely to improve clinical EFW accuracy. Published clinical EFW accuracies are likely to be similar to those obtained in clinical practice.     

The 2004 Italian legislation on the application of assisted reproductive technology: epilogue

Objective

To evaluate how the unique Italian fertility regulations (≤3 inseminated oocytes/cycle, transfer of all embryos, prohibition of embryo cryopreservation) affected outcomes of ART.

Study design

Case–control study from the Center of Reproductive Medicine, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. We compared outcomes of ART patients between five years before (n = 1791) and five years after (n = 2474) the implementation of the law.

Results

The mean embryo transfer (ET) rate was 3.1 ± 2.1 and 1.7 ± 1.1 before and after the law. Significantly more ICSI procedures were performed in women above 35 years old during the post-law period. The ET rate was higher before (88.6%) than after (80.5%) the law (OR 1.9, 95% CI 1.6, 2.2) especially in women >37 years undergoing ICSI (88.2 vs. 76.1%; OR 2.3, 95% CI 1.3, 4.2). The clinical pregnancy rates were practically unchanged but the proportion of triplet births significantly decreased after the law (10.3 vs. 4.1%, OR 2.7, 95% CI 1.4, 5.0).

Conclusion

In contrast to interim analyses, we found that the statutory obligation to transfer all available embryos produced from up to three inseminated oocytes reduced the ET rates, especially in older women, and decreased the triplet births rate.