Saline Hysteroscopy for Removal of Retained Intrauterine Contraceptive Devices in Early Pregnancy.

OBJECTIVE: Pregnancies complicated by a retained intrauterine device (IUD) are at increased risk for adverse outcomes such as miscarriage and preterm labour. There is limited evidence to guide the management of retained IUDs in pregnancy when the strings are not visible at the external cervical os. We describe a method for IUD retrieval in such cases. METHODS: Twenty-six patients underwent saline hysteroscopy with or without concurrent ultrasound guidance for retrieval of a retained IUD in early pregnancy between 2002 and 2015. We retrospectively evaluated procedural and pregnancy-related outcomes in this case series. RESULTS: The average gestational age at the time of the procedure was 11+0 weeks. Successful IUD retrieval occurred in 22 of 26 cases (84.6%). There were 23 live births, including 20 full term and three preterm deliveries. The average gestational age at delivery was 38+4 weeks. There was one miscarriage and one elective termination of pregnancy following the procedure. There were no complications directly related to the procedure. CONCLUSION: Saline hysteroscopy is a safe and effective method for retrieval of a retained IUD in early pregnancy. It appears that concurrent ultrasound guidance can facilitate IUD localization, but more cases are needed to confirm this. Pregnancy outcomes after IUD retrieval were favourable, with a low rate of miscarriage and preterm labour.

Intrauterine Adhesions Following Miscarriage: Look and Learn.

OBJECTIVE: To examine the incidence of intrauterine adhesions (IUA) following the management of miscarriage in women with previously documented normal uterine cavities. METHODS: We conducted a retrospective cohort study from two fertility clinics with standard practice protocols for evaluating the uterine cavity prior to infertility treatment and following clinical pregnancy loss. A database query and manual chart review identified 144 women with normal uterine cavities who experienced a miscarriage between January 2010 and November 2012 and returned to the clinic for follow-up hysteroscopy. Following documentation of a non-viable clinical pregnancy using transvaginal ultrasound, patients chose expectant, medical, or surgical management according to standardized clinical protocols. The primary outcome was the detection of IUA. Secondary outcomes included the presence of retained products of conception and various risk factors associated with the development of IUA. RESULTS: The incidence of IUA following early pregnancy loss was 6.3%. There were no significant differences in patient characteristics between those with and without IUA. There was a significant association between IUA and increasing uterine size, particularly in the presence of multiple gestation (P = 0.039). Mechanical suction dilatation and curettage (D&C) was a risk factor for IUA, but manual vacuum aspiration was not a risk factor (P = 0.003). Retained products of conception were found in 13.9% of study participants, and the incidence did not differ among management options. CONCLUSIONS: This appears to be the first documentation of IUA that were entirely attributable to the index miscarriage or its management. There appears to be an increased risk of IUA following D&C with larger uteri and multiple pregnancies and following mechanical suction D&C.

Curettage and Asherman's syndrome-lessons to (re-) learn?

OBJECTIVE: To investigate the noted cluster of cases of Asherman's syndrome in an 18-month period at an Early Pregnancy Assessment Centre at a tertiary care institution. METHODS: A practice audit was performed involving (a) a detailed chart review of the six index cases; and (b) compilation of treatment choices for all new patient referrals in the same 18-month time frame from July 2011 to December 2012. Diagnosis of Asherman's syndrome was made with a combination of clinical menstrual symptoms and hysteroscopic diagnosis of intrauterine adhesions. RESULTS: Of 1580 new patient referrals, 884 chose one of four forms of active management for early pregnancy failure. Six women (6/844, 0.7%) were subsequently found to have Asherman's syndrome. All six women (100%) underwent sharp curettage, and three (50%) had repeat curettage performed. No cases of Asherman's were reported following manual vacuum aspiration (0/191) or medical management with misoprostol (0/210). CONCLUSION: Asherman's syndrome remains a risk for those undergoing dilatation and curettage for management of spontaneous abortion and should be an important component of the informed consent for this procedure. Both sharp and repeated curettage remain important risk factors and should be employed judiciously. The evaluation of the common risk factors associated with these cases could target changes in practice.

Objectif : Se pencher sur le groupe de cas de syndrome d'Asherman qui ont été constatés sur une période de 18 mois au sein du centre d'évaluation de la grossesse précoce d'un établissement de soins tertiaires. Méthodes : Nous avons mené un audit de pratique mettant en jeu (a) une analyse détaillée des dossiers des six cas probants et (b) une compilation des choix de traitement pour toutes les nouvelles patientes de ce centre au cours de la même période de 18 mois (de juillet 2011 à décembre 2012). Un diagnostic de syndrome d'Asherman a été porté en fonction d'une combinaison de symptômes menstruels cliniques et d'un diagnostic hystéroscopique d'adhérences intra-utérines. Résultats : Chez les 1 580 nouvelles patientes de ce centre, 884 ont choisi l'une des quatre formes de prise en charge active de l'échec précoce de la grossesse. On a par la suite constaté la présence du syndrome d'Asherman chez six femmes (6/844, 0,7 %). Ces six femmes (100 %) ont subi une dilatation-curetage; trois d'entre elles (50 %) ont dû subir un deuxième curetage. Aucun cas de syndrome d'Asherman n'a été signalé à la suite d'une aspiration manuelle (0/191) ou d'une prise en charge médicale au moyen de misoprostol (0/210). Conclusion : Le syndrome d'Asherman demeure un risque pour les femmes qui subissent une dilatation-curetage aux fins de la prise en charge d'un avortement spontané et devrait constituer une composante importante du processus de consentement éclairé en ce qui concerne cette intervention. La tenue d'une dilatation-curetage et d'un deuxième curetage demeurent d'importants facteurs de risque; ces interventions devraient donc être utilisées de façon judicieuse. L'évaluation des facteurs de risque courants associés à ces cas pourrait permettre de cibler des changements en matière de pratique.

Telomere length and reproductive aging.

BACKGROUND: Rate of reproductive aging may be related to rate of biological aging. Thus, indicators of aging, such as short telomere length, may be more frequent in women with a history suggestive of premature reproductive senescence. METHODS: Telomere-specific quantitative PCR was used to assess telomere length in two groups of women with evidence of reproductive aging: (i) patients with idiopathic premature ovarian failure (POF, N = 34) and (ii) women with a history of recurrent miscarriage (RM, N = 95); and two control groups: (1) women from the general population (C1, N = 108) and (2) women who had a healthy pregnancy after 37 years of age (C2, N = 46). RESULTS: The RM group had shorter age-adjusted mean telomere length than controls (8.46 versus 8.92 kb in C1 and 9.11 kb in C2, P = 0.0004 and P = 0.02 for C1 and C2, respectively), although short telomeres were not confined to subsets of this group known to have experienced single or multiple trisomic pregnancies. Although sample size is limited, mean telomere length in the POF group was significantly longer than that in C1 (9.58 versus 8.92 kb, P = 0.01). CONCLUSIONS: Women experiencing RM may have shorter telomeres as a consequence of a more rapid rate of aging, or as a reflection of an increased level of cellular stress. Longer telomere length in the POF group may be explained by abnormal hormone exposure, slow cell division rates or autoimmunity in these women. Despite small sample sizes, these results suggest that different manifestations of reproductive aging are likely influenced by distinct physiological factors.

Estrogen receptor alpha gene polymorphisms are associated with idiopathic premature ovarian failure.

OBJECTIVE: To assess the role of hormone receptor/binding protein variants in genetic predisposition to premature ovarian failure (POF). DESIGN: Case-control study. SETTING: Academic. PATIENT(S): Fifty-five POF patients, 107 control women from the general population, and 27 control women who had proven fertility after age 37. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Allele distributions in cases and controls were assessed for genetic association. RESULT(S): Allele distributions of polymorphisms at the androgen receptor (AR) gene, estrogen receptor beta (ESR2) gene, sex hormone-binding globulin (SHBG) gene, and FSH receptor (FSHR) gene did not differ between patients and controls. At a repeat in a promoter of the estrogen receptor alpha(ESR1) gene, POF patients had fewer (<18) short repeat alleles than did controls (P=.004 vs. combined controls). Genotypes consisting of two short alleles were found in 36.4% of control women but only 5.5% of POF patients (P<.0001 vs. combined controls). The ESR1 repeat may confer risk for POF in a simple dominant manner in which carriers of a long repeat have a relative risk of 9.7 (95% CI = 2.6 - 35.6). CONCLUSION(S): Polymorphisms at the ESR1 gene are associated with POF in this patient population, while those in AR, ESR2, SHBG, and FSHR showed no association. Further studies are necessary to confirm these findings in larger patient samples and to identify the specific predisposing lesion.

Skewed X-chromosome inactivation is associated with primary but not secondary ovarian failure.

Premature ovarian failure (POF) is the occurrence of menopause before the age of 40, and may present with either primary or secondary amenorrhea. Numerous cases of POF in women with X-chromosome deletions or translocations have been reported; thus, it is possible that smaller rearrangements undetectable by conventional cytogenetics may contribute to POF in some patients. In females with an abnormal X chromosome, cells with inactivation of the normal X may be selected against, causing skewed X-chromosome inactivation (XCI). We therefore assessed XCI by methylation sensitive restriction digestion and PCR amplification at the androgen receptor (AR) locus, in 4 primary and 55 secondary POF patients and 109 control women. In samples heterozygous at AR and therefore informative for the skewing assay, the frequency of skewed XCI among the women with secondary amenorrhea was identical to that in control women, with 4 out of 48 (8.3%) secondary ovarian failure patients and 8 out of 97 (8.2%) control women having > or =90% skewing. Notably, all three primary amenorrhea patients that were informative at AR had skewed XCI > or =90% (P = 0.001 vs. control women; Fisher's exact test). To investigate whether X-chromosome copy number alterations were responsible, DNA from selected patients with skewed XCI was examined by high resolution DNA microarray, however no potential regions of DNA addition or deletion were confirmed by FISH or PCR. X-chromosome abnormalities undetectable by array, or reduced follicular pool due to an early trisomic rescue event, may explain the skewed XCI observed in POF patients presenting with primary amenorrhea.

FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of menopause before the age of 40 and affects 1% of the female population. Whereas the etiology of POF is largely unexplained, FMR1 premutation carriers are known to be at increased risk of POF compared with the general population. The FMR1 premutation alleles have 55-200 copies of a CGG repeat in the 5' untranslated region of the FMR1 gene. However, functional effects on gene expression may occur even for repeat sizes in what has been considered the "normal" range. To evaluate the role of the FMR1 repeat in POF, repeat sizes were examined in 53 women with idiopathic POF, 161 control women from the general population, and 21 women with proven fertility at an advanced maternal age. A significant increase in the number of FMR1 alleles between and including 35 and 54 CGG repeats was found in the POF patient population; 15 of 106 (14.2%) POF alleles were between and including 35 and 54 repeats, whereas only 21 of 322 (6.5%) alleles in the general population (P=0.02) and 2 of 42 (4.8%) alleles from women with proven late fertility (P=0.09) were of this size (P=0.01 versus combined controls). The effect was also significant for comparisons of genotype repeat size (repeat size weighted by the relative activity of the two FMR1 alleles) and biallelic mean (average size of the two alleles). These results are clinically relevant and suggest that the FMR1 gene plays a more significant role in the incidence of POF than has previously been thought.

A randomized, double-blind, multicenter study comparing a starting dose of 100 IU or 200 IU of recombinant follicle stimulating hormone (Puregon) in women undergoing controlled ovarian hyperstimulation for IVF treatment.

PURPOSE: To compare the efficiency and efficacy of two starting doses of recombinant FSH (follitropin-beta, Puregon) in women undergoing IVF treatment. METHODS: This prospective, randomized, double-blind, multicentric (N = 6) study included 192 women undergoing IVF using the long protocol of GnRH agonist who received either 100 IU or 200 IU of r-FSH per day. Gonadotropin dose adjustment was allowed after day 4 of stimulation. RESULTS: The average (SD) number of oocytes retrieved was 10.9 (5.4) and 12.2 (5.6) in the 100 IU and 200 IU group respectively (p = 0.067). The total doses of Puregon administered were 1887 IU and 2559 IU in the 100 IU and 200 IU group respectively. The number of transferable embryos, and the rates of pregnancies, cancelled cycles, miscarriages and adverse events including OHSS were comparable between the two groups. CONCLUSIONS: Women undergoing IVF have similar outcomes whether recombinant FSH is commenced in a dose of 100 IU or 200 IU for the first 4 days of stimulation.