Early versus late hCG administration to trigger ovulation in mild stimulated IUI cycles: a randomized clinical trial

Objectives

To verify non-inferiority of the clinical pregnancy rate of Early hCG administration (leading follicle sizes within 16.0–16.9 mm in diameter) compared to Late hCG administration (leading follicle sizes within 18.0–18.9 mm in diameter).

Study design

Prospective randomized trial. Six hundred and twelve infertile women candidates for intrauterine insemination (IUI) received HP-hMG 75 IU/day SC from cycle days 4 to 8 and then as per ovarian response. Ovulation was randomly triggered (hCG 5000 IU, IM) when the leading follicle diameter ranged between either 16.0 and 16.9 mm (Early hCG group, n = 227) or 18.0 and 18.9 mm (Late hCG group, n = 207) and IUI was performed approximately 36 h later.

Results

Whereas population and sperm characteristics were comparable in both groups, the number of follicles ≥14 mm in diameter (P < 0.007) and serum estradiol levels (P < 0.001) on the day of hCG were lower in the Early versus the Late hCG groups. Clinical (11.9% versus 12.1%) and ongoing (11.0% versus 8.6%) pregnancy rates per randomized women were similar in the two groups and statistical non-inferiority of clinical and ongoing pregnancy rates was demonstrated.

Conclusion

These results suggest that hCG administered when the largest follicle size reaches 16.0–16.9 mm leads to similar clinical and ongoing pregnancy rates as when it reaches 18.0–18.9 mm in IUI cycles.     

Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility

Objective

To compare two different gonadotropin preparations, human menopausal gonadotropin (hMG) and recombinant follicle-stimulating hormone (rFSH), combined with clomiphene citrate (CC) in women with unexplained infertility undergoing intrauterine insemination (IUI).

Study design

In this prospective clinical trial, couples prepared for IUI cycles were randomly allocated to two groups either to receive CC and hMG (group A, n = 127) or CC and rFSH (group B, n = 132) for ovarian stimulation. Outcomes including rates of clinical pregnancy, miscarriage, OHSS, multiple pregnancy, cancelation, and live birth were compared between groups.

Results

Duration of gonadotropin therapy was significantly shorter in group B (5.1 ± 0.84 vs. 4.7 ± 0.8 days, CI = 95%, P < 0.001). The total dose of administered gonadotropin was also significantly lower in group B (386.9 ± 68.2 vs. 348.2 ± 56.3 IU, CI = 95%, P < 0.001). Dominant follicle number (>17 mm), mean follicular diameter, and endometrial thickness on the day of hCG injection were similar. Clinical pregnancy, multiple pregnancies, abortion, live birth, ovarian hyperstimulation syndrome (OHSS), and cancelation rates were not statistically different between the groups.

Conclusion

IUI cycles in which rFSH had been administered may require shorter duration and a lower total gonadotropin dose.     

Long term outcome in subfertile couples with isolated cervical factor

Objective

A previous randomized clinical trial (RCT) compared immediate treatment with intrauterine insemination (IUI) to expectant management for six months in subfertile couples with an isolated cervical factor. That study showed higher ongoing pregnancy rates in couples receiving intrauterine insemination. The current study compared the long-term effectiveness and costs of this intervention.

Study design

We followed all couples (N = 99) who were previously included in the RCT for three years after randomization and registered pregnancies and treatments. After the initial trial period, couples in both groups were offered further treatment according to local protocol. The primary outcome was an ongoing pregnancy after three years.

Results

After three years, there were 36 ongoing pregnancies in the immediate IUI group (N = 51 couples) and 38 ongoing pregnancies in the expectant management group (N = 48 couples). The ongoing pregnancy rates were 71% and 79% respectively (RR 0.89 (95% confidence interval (CI) 0.7–1.1)).

Conclusions

In couples with an isolated cervical factor, a treatment strategy including immediate treatment with IUI does not result in higher ongoing pregnancy rates on the long term. Initial expectant management is therefore justified in these couples and identifying a cervical factor by a post-coital test is unnecessary.     

Effect of cervical mucus aspiration before intrauterine insemination

Objective

To determine whether cervical mucus aspiration before intrauterine insemination (IUI) has any effect on clinical pregnancy rates.

Method

The outcomes of 186 IUI cycles in 95 consecutive patients in whom mucus was aspired prior to IUI were compared retrospectively with those of 1057 IUI cycles in 505 women.

Results

The pregnancy rate was 15.1% (28 pregnancies for 186 cycles) in the cervical mucus aspiration group and 9.9% (105 pregnancies for 1057 cycles) in the control group (P = 0.05). Mucus aspiration led to significantly increased pregnancy rates for women with unexplained infertility (24% in the aspiration group vs 9.5% in the control group; P = 0.04).

Conclusion

Cervical mucus aspiration before IUI might improve clinical pregnancy rates by yet-to-be-defined mechanisms.     

Effectiveness of GnRH antagonist in intrauterine insemination cycles

Objective

To evaluate the effectiveness of GnRH antagonists in women undergoing controlled ovarian stimulation and intrauterine insemination cycles (COS/IUI).

Study design

Randomized controlled trial. Recruited women were randomized into two groups: GnRH antagonist and control group. The primary outcomes were incidence of premature LH surge and clinical pregnancy rates.

Results

One hundred and forty-one consecutive women were included in the study, with 70 in the antagonist group and 71 in the control arm. The baseline clinical characteristics were similar in both groups. The incidence of premature LH surge and premature luteinization was lower in the antagonist group as compared to the control group (5% vs. 10.3%, P = 0.45 and 5% vs. 13.8, P = 0.31) but not statistically significant. The clinical pregnancy rates were lower in the antagonist group (2.8% vs. 10%, P = 0.12), which was also not statistically significant.

Conclusion

The addition of GnRH antagonist during controlled ovarian stimulation and intrauterine insemination cycles does not lead to improvement in clinical pregnancy rates.     

Vaginal progesterone supplementation has no effect on ongoing pregnancy rate in hCG-induced natural frozen–thawed embryo transfer cycles

Objective

The purpose of this study is to assess the effect of luteal phase supplementation (LPS) on pregnancy rates in human chorionic gonadotropin (hCG)-induced natural frozen–thawed (FET) cycles.

Study design

All performed hCG-induced natural FET cycles from January 2006 until August 2007 were retrospectively identified. The study group consisted of 452 cycles: 243 supplemented with progesterone administration (600 mg natural micronized progesterone in three separate doses) and 209 without progesterone. Analysis was limited to cycles where embryos were cryopreserved on day 3. Final oocyte maturation was achieved by hCG when endometrial thickness of ≥7 mm and a follicle of 17 mm were present on ultrasound.

Results

No statistically significant differences were observed in ongoing pregnancy rate between the two groups (22% versus 21%, p = 0.8; difference +1%; 95% confidence interval (CI): −6.5 to +8.7). The non-significant effect of the presence or not of luteal support on pregnancy rate was confirmed by logistic regression (odds ratio (OR): 0.9, 95% CI: 0.54–1.47, P = 0.64). A previous pregnancy following fresh embryo transfer (OR: 6.04, 95% CI: 3.63–10.02, P = 0.001) and increased endometrial thickness (OR: 1.25, 95% CI: 1.11–1.41, P = 0.001) significantly affected the achievement of ongoing pregnancy, whereas the association between embryo score and achievement of pregnancy was marginally significant (OR:0.28, 95% CI: 0.08–0.97, P = 0.05).

Conclusion

There is no convincing evidence to support the use of LPS in hCG-induced natural FET cycles, since there is no luteal phase defect. Further prospective randomized studies are necessary to confirm these findings.     

Quality of life of infertile Tunisian couples and differences according to gender

Objective

To compare quality-of-life gender differences within infertile couples from Tunisia and between infertile couples and controls.

Methods

The present case–control study included 100 couples with primary infertility who, during 2009, underwent assisted reproductive technology at Farhat Hached Hospital in Sousse, Tunisia, and 100 control couples. The 36-item Short-Form Health Survey (SF-36) was administered to assess quality of life.

Results

Compared with male controls, men in the infertility group had lower scores in the mental dimension (P = 0.020), social functioning (P = 0.007), and role–emotional (P < 0.001) categories of the SF-36. Women in the infertility group had lower mental and physical dimension scores (P < 0.001) and lower vitality (P = 0.022), social functioning (P < 0.001), role–emotional (P < 0.001), and mental health (P < 0.001) scores than female controls. Within infertile couples, female partners had lower total (P = 0.01) and mental dimension (P < 0.001) scores than their spouses. Delay of the first consultation was correlated with bodily pain, vitality, and mental health among women in the infertility group.

Conclusion

Women in infertile couples had a lower quality of life than their spouses, and infertile couples had a lower quality of life than controls. These findings confirm the need for psychological support for infertile couples.     

A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III–IV endometriosis

Objective

To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis.

Study design

Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot—3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients).

Results

Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P = 1, RR = 0.94, 95% CI = 0.57–1.55), endometrioma relapse (P = 0.67, RR = 1.29, 95% CI = 0.66–2.50), and pregnancy rate in infertile women (P = 0.80, RR = 0.81, 95% CI = 0.37–1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P = 0.79 and P = 0.51, respectively, using Mantel–Haenzsel logrank test).

Conclusion

Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.     

Evaluation of FAS and caspase-3 in the endometrial tissue of patients with idiopathic infertility and recurrent pregnancy loss

Objective

To investigate expression of BcL-2, FAS, FAS ligand (FASL) and cleaved caspase-3 in the endometrial tissue of women with idiopathic infertility (with two consecutive failed cycles of in vitro fertilization) and women with idiopathic recurrent pregnancy loss. The control group consisted of fertile women.

Study design

Endometrial tissue samples from fertile women (n = 25), women with idiopathic infertility (n = 25) and women with idiopathic recurrent pregnancy loss (n = 25) were collected on the seventh or eighth postovulatory day of their menstrual cycles for evaluation. Expression of BcL-2, FAS, FASL and cleaved caspase-3 was assessed using immunohistochemical methods.

Results

Expression of BcL-2 and FAS was significantly higher and lower, respectively, in the women with idiopathic infertility than in the other groups (p < 0.01). Expression of cleaved caspase-3 was significantly lower in the women with idiopathic infertility than in the other groups (p < 0.01). Expression of FASL was similar in all three groups.

Conclusion

Disturbances in endometrial apoptosis may be a contributing factor in patients with idiopathic infertility and recurrent pregnancy loss.     

Bacterial vaginosis and infertility: cause or association?

Objectives

To estimate the prevalence of bacterial vaginosis (BV) in infertile women and evaluate the effect of treatment of BV on the pregnancy rate in patients with polycystic ovarian disease (PCOD) and unexplained infertility.

Study design

Cohort study conducted at the Department of Obstetrics and Gynecology in collaboration with the Microbiology Department of Sohag University Hospital, Egypt. All eligible women with female factor infertility (n = 874) were enrolled and all asymptomatic fertile women (n = 382) attending the family planning clinic of the study hospital were recruited as a control group. The study was in two phases: the first included screening all participants for BV after Gram-staining of the vaginal discharge. The second phase was concerned with evaluating the effect of treatment of BV on the cumulative pregnancy rate (CPP) in patients with PCOD (group I; n = 278) and unexplained infertility (group II; n = 170). Each group was divided into three sub-groups: groups Ia (n = 129) and IIa (n = 73) were BV positive and treated for BV; groups Ib (n = 61) and IIb (n = 49) were BV positive and did not receive treatment for BV, and groups Ic (n = 88) and IIc (n = 48) were BV negative. The prevalence of BV was compared using the Chi-square. The long rank test of Kaplan-Meier life table analysis was used to compare the CPR. A multivariate regression model was designed to define the most significant variable which affected the pregnancy rate in patients with PCOD.

Results

The prevalence of BV was significantly higher in infertile than fertile women (45.5% vs 15.4%). The highest prevalence was found in patients with PCOD (60.1%) and unexplained infertility (37.4%). The CPR in both patients with PCOD and unexplained infertility were significantly higher in the patients who were treated for BV. Regression model showed that BV was one of the significant factors interfering with pregnancy.

Conclusions

BV is strongly implicated in female infertility and is probably an underestimated cause of unexplained infertility. Screening and treatment of BV in patients with PCOD and unexplained infertility improved the pregnancy rate considerably.     

Maternal hyperglycemia and adverse pregnancy outcomes in Dar es Salaam,Tanzania

Objective

To evaluate maternal glucose levels during pregnancy as a predictor of adverse perinatal outcomes in Dar es Salaam, Tanzania.

Methods

Random blood glucose measurements were analyzed from 3383 pregnant women enrolled in a randomized trial to assess the impact of multivitamins on pregnancy outcomes in Dar es Salaam between August 2001 and July 2004. Information on maternal and neonatal morbidity was recorded at monthly study visits, delivery, and 6 weeks postpartum. Binomial regression and generalized estimating equations were used to determine the relationship between elevated glucose (> 7.8 mmol/L) and pregnancy outcomes.

Results

In total, 25 women had elevated glucose (0.7%). Hyperglycemia was associated with an increased risk of delivery before 37 weeks [relative risk (RR), 2.11; 95% confidence interval [CI], 1.07–4.13; P = 0.03), delivery before 34 weeks (RR, 4.15; 95% CI, 1.43–12.03, P = 0.009), incident gestational hypertension (RR, 2.90; 95% CI, 1.24–6.76; P = 0.01), low birth weight (RR, 2.87; 95% CI, 1.18–6.99; P = 0.02), reduced newborn head circumference (mean difference, –1.57; 95% CI, –2.51 to − 0.62; P = 0.001), and fetal loss (RR, 3.38; 95% CI, 1.13–10.08; P = 0.03).

Conclusion

Maternal hyperglycemia is uncommon among pregnant Tanzanian women, but nonetheless seems to increase the risk of several adverse perinatal outcomes.     

Factors associated with the use of prenatal corticosteroids in the management of preterm delivery in Chinese hospitals

Objective

To assess the prevalence of the use of prenatal corticosteroids (PCS) in the management of preterm delivery and the factors associated with PCS administration.

Methods

A secondary analysis was performed of a cross-sectional study conducted in 21 Chinese healthcare facilities between November 2010 and January 2011. The medical records of women who delivered preterm were reviewed. Associations between PCS administration and individual and organizational-level factors were determined.

Results

The study population comprised 659 women who delivered at 20 facilities. PCS were given to 158 (68.1%) of 232 women delivering after 27–34 weeks of pregnancy and 119 (27.9%) of 427 delivering after 35–36 weeks. Teenaged girls were less likely to receive PCS after 27–34 weeks than were women aged 20–35 years (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.07–0.70). Among women who delivered after 35–36 weeks, the odds of receiving PCS were lower in urban hospitals than in periurban or rural hospitals (OR 0.04; 95% CI 0.00–0.44), and there was significant hospital-level variance with regard to the administration of PCS (P < 0.05).

Conclusion

Generally, PCS were underprescribed to women at risk of preterm delivery and many women received the treatment after 35–36 weeks of pregnancy, when it might not have been effective.     

Trends in preterm birth in singleton deliveries in a Hong Kong population

Objective

To examine trends in preterm birth and its relationship with perinatal mortality in Hong Kong.

Methods

In a retrospective cohort study, data were reviewed from singletons delivered between 1995 and 2011 at a university teaching hospital. Trends in preterm birth (between 24 and 36 weeks of pregnancy), perinatal mortality, and subtypes of preterm birth (spontaneous, iatrogenic, and following preterm premature rupture of membranes [PPROM]) were examined via linear regression.

Results

There were 103 364 singleton deliveries, of which 6722 (6.5%) occurred preterm, including 1835 (1.8%) early preterm births (24–33 weeks) and 4887 (4.7%) late preterm births (34–36 weeks). Frequency of preterm birth remained fairly consistent over the study period, but that of spontaneous preterm birth decreased by 25% (β = –0.83; P < 0.001), from 4.5% to 3.8%. Frequency of preterm birth following PPROM increased by 135% (β = 0.82; P < 0.001), from 0.7% to 1.7%. The perinatal mortality rate decreased from 56.7 to 37.0 deaths per 1000 deliveries before 37 weeks (β = –0.16; P = 0.54). Early preterm birth contributed to 16.0% of all deaths.

Conclusion

Although the overall rate of preterm birth in Hong Kong has remained constant, the frequencies of its subtypes have changed. Overall perinatal mortality is gradually decreasing, but early preterm birth remains a major contributor.     

Factors influencing delivery mode for nulliparous women with a singleton pregnancy and cephalic presentation during a 17-year period

Objective

To evaluate the effects of maternal age, induction of labour, epidural analgesia and birth weight on mode of delivery in nulliparous women with a singleton pregnancy and cephalic presentation at ≥36 weeks gestation, and to describe how these factors and their influence have changed over a 17-year period from 1989 to 2005.

Study design

The study was conducted in the obstetric department of a university teaching hospital in Ireland. Of 45,647 women delivered, 14,867 were nulliparous with a singleton pregnancy and cephalic presentation and undergoing labour at ≥36 weeks gestation, and were included in the study. The main outcome measures were the influence of maternal age, induction of labour, epidural analgesia and birth weight on the mode of delivery. Multinomial logistic regression analysis for type of delivery and the associated explanatory variables and trend analysis of these variables were performed.

Results

There was a significant progressive increase in both unplanned abdominal delivery and instrumental vaginal delivery, with advancing maternal age. Induction of labour increased the risk of unplanned abdominal delivery (OR 1.92; 95% CI 1.73–2.14). Epidural analgesia was associated with an increased risk of instrumental vaginal delivery (OR 4.68; 95% CI 4.18–5.25), and unplanned abdominal delivery (OR 2.29; 95% CI 1.98–2.66). Mothers of infants with birth weight ≥4.5 kg were less likely to be delivered by instrumental vaginal delivery (OR 0.60; 95% CI 0.41–0.88), than mothers delivering infants in the 2.50–4.49 kg birth weight category. Between 1989 and 2005 there was a significant increase in maternal age (P = 0.0001), birth weight (P = 0.042) and unplanned abdominal delivery rates (P = 0.0004), and a reduction in instrumental vaginal delivery rates (P = 0.0013).

Conclusions

These data demonstrate that the increasing trend of unplanned abdominal delivery in nulliparous women with a singleton pregnancy and cephalic presentation may be partially explained by advancing maternal age, and other obstetric factors also play a significant role.     

GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial

Objective

To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.

Study design

This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0–4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II).

Results

Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P = NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P = NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P = NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P = 0.03).

Conclusions

Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.     

Idiopathic urinary findings and fetal growth restriction in low risk pregnancy

Objective

To determine whether maternal urinary findings in the first trimester of pregnancy are associated with fetal growth restriction.

Study design

The prevalence of urinary findings in singleton pregnancies complicated by fetal growth restriction were compared with a low-risk control group of pregnancies who gave birth to normal weight babies, in the same condition.

Results

There were significant statistical differences in the mean gestational age (p < 0.001), isolated asymptomatic bacteriuria (p < 0.001), hematuria (p = 0.002, OR = 6.6, CI = 1.8–24.2) and proteinuria (p = 0.016, OR = 4.1, CI = 1.2–13.3). There was no recognizable relation between ketonuria and fetal growth restriction.

Conclusion

Our data showed a relation between the increase of adverse pregnancy outcomes, including fetal growth restriction, and hematuria, proteinuria and asymptomatic bacteriuria. Appropriate monitoring of pregnant women using these findings may be helpful in the identification of more complications.     

Fresh blastocyst transfer as a clinical approach to overcome the detrimental effect of progesterone elevation at hCG triggering: a strategy in the context of the Italian law

Objective

To retrospectively evaluate whether fresh day-5 embryo transfer could overcomes the detrimental effect of subtle progesterone elevations at hCG administration on pregnancy outcomes in women undergoing ovarian hyperstimulation for IVF/ICSI cycles.

Study design

Retrospective study of 204 infertile patients aged 23–44 years who underwent IVF/ICSI treatment and fresh blastocyst transfer under the Italian law (embryos cryopreservation cannot be planned in advance). Women were divided into those with a progesterone level <1.5 ng/ml and those with a progesterone concentration ≥1.5 ng/ml at hCG triggering. The clinical pregnancy rate (CPR) after blastocyst transfer was the primary outcome.

Results

Age, body mass index (BMI), antral follicle count, anti-Mullerian hormone (AMH) and FSH values, mean number of stimulation days, ratio of GnRH agonist and antagonist cycles and total dose of gonadotrophins administered did not differ between the two groups. Serum estradiol and number of retrieved oocytes were significantly increased in the group with elevated progesterone and a significantly higher number of oocytes was used in this group. Fertilization rate, percentage of top quality embryos, and number of transferred blastocysts were similar in the two groups. The CPR was significantly higher in women with progesterone levels <1.5 ng/ml at hCG (50%) compared with women with progesterone concentration ≥1.5 ng/ml (33.3%) (odds ratio = 2.00, 95% confidence interval 1.07–3.75).

Conclusions

A fresh blastocyst transfer does not completely overcome the detrimental effect of progesterone rise at hCG on IVF/ICSI pregnancy outcomes.     

The effect of a policy change on late termination of pregnancy in Israel

Objective

To compare approval rates of late termination of pregnancy (LTOP) requests before and after a policy change in Israel in late 2007.

Methods

In a retrospective study, LTOP requests and board decisions from 2002–2007 (group 1) were compared with those from 2007–2012 (group 2) at 3 university-affiliated medical centers in Israel. Reasons for application, approval, or rejection were compared between the groups.

Results

There were 552 applications for LTOP. The overall approval rate for LTOP and the specific approval rate per medical indication did not differ significantly between the groups. The rate of requests due to confirmed genetic anomalies decreased from 18.4% in group 1 to 11.3% in group 2 (P = 0.03). Compared with group 1, the rate of rejection for intrauterine infection increased from 8.3% to 26.3% (P = 0.2), and that for pregnancy complications decreased from 62.5% to 35.0% (P = 0.2) in group 2 but these differences were not statistically significant. Requests due to structural anomalies were declined because they were considered to be minor cardiac, renal, cerebral, or skeletal anomalies.

Conclusion

The more stringent 2007 criteria for approving requests for LTOP did not affect the rate of rejection of requests due to structural anomalies between the 2 time periods.     

Human chorionic gonadotropin as a measure of pregnancy duration

Objective

To compare gestational age (GA) estimates in early pregnancy, determined by last menstrual period (LMP), human chorionic gonadotropin (hCG) concentration, ultrasound crown–rump length (Hadlock formula), and ovulation day (luteinizing hormone surge plus 1 day).

Methods

Female volunteers seeking to conceive (at 5 US sites) collected daily early-morning urine for up to 3 menstrual cycles. Pregnant women underwent ultrasound dating scans. Conception cycle urine was quantitatively assessed for luteinizing hormone and hCG. Summary statistics for GA using each reference method were determined (n = 131).

Results

Correlation between GA determined by ultrasound and ovulation day was excellent (maximum difference 10 days); however, pregnancies dated by ultrasound were 3 days advanced. The difference between LMP estimates and estimates based on ovulation day or ultrasound was 9 and 12 days, respectively. A uniform rise in hCG on each day of pregnancy was seen using all reference methods. The accuracy of hCG measurement in determining the week since conception was more than 93%.

Conclusion

Methods for establishing pregnancy duration vary in their accuracy and their GA estimates. The rise in hCG concentration in early pregnancy is uniform and therefore hCG levels provide the most accurate, early estimation of GA in single, viable pregnancies.ClinicalTrials.gov:NCT01077583     

Intracytoplasmic morphologically selected sperm injection is beneficial in cases of advanced maternal age: a prospective randomized study

Objective

To evaluate advanced maternal age as a rationale for performing intracytoplasmic morphologically selected sperm injection (IMSI).

Study design

This study included couples undergoing intracytoplasmic sperm injection (ICSI) as a result of advanced maternal age (≥37 years old). Sample size calculations were based on the assumption that a 15% difference in implantation rate would mean a clinically significant difference. To achieve this difference, 33 cycles would be needed in each treatment arm (with a significance level of 5% and power of 85%). Couples were randomly allocated to one of two sperm selection procedures (ICSI, n = 33; or IMSI, n = 33). Sperm selection in the ICSI group was analyzed under a magnification of 400×. Sperm selection in the IMSI group was analyzed under high magnification of 6600×. The groups were compared with regard to the outcome of the cycles.

Results

IMSI cycles showed significantly higher implantation (4/33, 12.1% vs. 18/47, 38.3%, p = 0.026) and pregnancy (4/29, 13.8 vs. 18/30, 60.0%, p < 0.001) rates. The IMSI procedure positively influenced the blastocyst formation rate (RC: 15.00, R²: 49.9%, p = 0.001) and implantation rate (RC: 24.04, R²: 9.6, p = 0.027), and was determinant to the increased odds of pregnancy (OR: 9.0, CI: 2.17–37.38, p = 0.001).

Conclusion

It seems that the injection of a morphologically normal spermatozoon overcomes the low oocyte quality in older women, resulting in improved embryo quality and in a 9-fold increase in the clinical pregnancy rate in couples with advanced maternal age.