Best Practice & Research Clinical Obstetrics & Gynaecology最新文献

As endometriosis is recognized as a contributing factor to infertility, prompting couples to embark on Assisted Reproductive Technology (ART) treatments, it becomes crucial to comprehend the extent and way this condition can affect success rates. Natural conception data reveal lower success rates for women with endometriosis, yet the same cannot be extrapolated to the outcomes of in vitro fertilization (IVF). In recent years, advancements in the ART process, particularly the distinct stages of the IVF pathway and investigations into embryo quality have shown a comparable rate of embryonic quality and chromosomal normalcy (euploidy) between embryos obtained from individuals with or without endometriosis. Thus, the primary question that lingers relates to the functionality of the endometrium. This review addresses whether endometriosis can influence endometrial receptivity and implantation rates.

Preeclampsia (PE) is a multiorgan disorder that complicates around 2–8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a clinical syndrome characterized by hypertension secondary to systemic inflammation, endothelial dysfunction, and syncytiotrophoblast stress leading to hypertension and multiorgan dysfunction.

The uterine arteries are the main blood vessels that supply blood to the uterus. They give off branches and plays an important role in maintaining blood supply during pregnancy. The arcuate artery originates from the uterine artery and runs medially through the myometrium. The arcuate arteries divide almost directly into anterior and posterior branches, from which the radial artery leads directly to the uterine cavity during their course. Near the endometrium-myometrium junction, the radial artery generates spiral arteries within the basal layer and functional endometrium. The walls of radial and spiral arteries are rich in smooth muscle, which is lost when trophoblast cells invade and become large-caliber vessels. This physiological transformation of uteroplacental spiral arteries is critical for successful placental implantation and normal placental function.

In normal pregnancy, the luminal diameter of the spiral arteries is greatly increased, and the vascular smooth muscle is replaced by trophoblast cells. This process and changes in the spiral arteries are called spiral artery remodeling. In PE, this genetically and immunologically governed process is deficient and therefore there is decreased vascular capacitance and increased resistance in the uteroplacental circulation. Furthermore, this defect in uteroplacental spiral artery remodeling is not only associated with early onset PE, but also with fetal growth restriction, placental abruption, and spontaneous premature rupture of membranes. Doppler ultrasound allows non-invasive assessment of placentation, while the flow impedance decreases as the pregnancy progresses in normal pregnancies, in those destined to develop preeclampsia the impedance is increased.

Cardiovascular disease (CVD) is the leading cause of premature death and disability for female individuals around the world and the rates are increasing in those aged 35–44 years. Certain pregnancy complications (Pregnancy-associated Cardiovascular Risks (P-CVR))are linked to an increased risk of future CVD making pregnancy and the postpartum period as an ideal time to screen individuals for underlying, often unrecognized, cardiovascular risk factors. Pregnancy complications associated with an increased risk of future CVD including the hypertensive disorders of pregnancy, gestational diabetes, idiopathic preterm birth, delivery of a growth restricted baby and a placental abruption that leads to delivery. A number of guidelines and research groups recommend postpartum CVR screening, counseling and lifestyle intervention for all those who have had one or more of P-CVRs starting within the first six months postpartum. An individualized plan for postpartum screening should be created with the individual and lifestyle interventions discussed.

High-intensity focused ultrasound (HIFU) has emerged as a promising uterus-sparing and possibly fertility-sparing treatment modality for women with adenomyosis, especially those who desire to conceive. We conducted this systematic review and performed a meta-analysis on clinical studies aimed to improve reproduction in women with adenomyosis. After extensive search of PubMed and CNKI, we identified 10 studies published in English and Chinese involving a total of 557 patients with adenomyosis who desired to conceive after HIFU treatment. We found a pooled estimate of pregnancy rate of 53.4% and of the live birth rate of 35.2%, and there was a substantial heterogeneity among these studies. While there is a potential for HIFU treatment to improve fertility for patients with adenomyosis who desired to conceive, such evidence is very weak as of now. Comparative studies with much higher methodological rigor, preferably randomized clinical trials, are badly needed to further illuminate this issue.

Preeclampsia is a pregnancy-specific disorder, and it is a leading cause of maternal and perinatal morbidity and mortality. The application of pharmacogenetics to antihypertensive agents and dose selection in women with preeclampsia is still in its infancy. No current prescribing guidelines from the clinical pharmacogenetics implementation consortium (CPIC) exist for preeclampsia. Although more studies on pharmacogenomics are underway, there is some evidence for the pharmacogenomics of preeclampsia therapies, considering both the pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs used in preeclampsia. It has been revealed that the CYP2D6*10 variant is significantly higher in women with preeclampsia who are non-responsive to labetalol compared to those who are in the responsive group. Various genetic variants of PD targets, i.e., NOS3, MMP9, MMP2, TIMP1, TIMP3, VEGF, and NAMPT, have been investigated to assess the responsiveness of antihypertensive therapies in preeclampsia management, and they indicated that certain genetic variants of MMP9, TIMP1, and NAMPT are more frequently observed in those who are non-responsive to anti-hypertensive therapies compared to those who are responsive. Further, gene–gene interactions have revealed that NAMPT, TIMP1, and MMP2 genotypes are associated with an increased risk of preeclampsia, and they are more frequently observed in the non-responsive subgroup of women with preeclampsia. The current evidence is not rigorous enough for clinical implementation; however, an institutional or regional-based retrospective analysis of audited data may help close the knowledge gap during the transitional period from a traditional approach (a “one-size-fits-all” strategy) to the pharmacogenomics of preeclampsia therapies.

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in their first trimester of pregnancy to allow timely therapeutic intervention. The use of low-dose aspirin initiated before 16 weeks of gestation can significantly reduce the rate of preterm preeclampsia by 62 %. Effective screening recommended by the Fetal Medicine Foundation (FMF) consists of a combination of maternal risk factors, mean arterial pressure, uterine artery pulsatility index (UtA-PI) and placental growth factor (PLGF). The current model has detection rates of 90 %, 75 %, and 41 % for early, preterm, and term preeclampsia, respectively at 10 % false-positive rate. Similar risk assessment can be performed during the second trimester in all pregnant women irrespective of first trimester screening results. The use of PLGF, UtA-PI, sFlt-1 combined with other investigative tools are part of risk assessment.

Globally obesity is increasing especially in the reproductive age group. Pregnant women with obesity have higher complication and intervention rates. They are also at increased risk of stillbirth and intrapartum complications. Although organisations like NICE, RCOG, ACOG and WHO have published guidelines and recommendations on care of pregnant women with obesity the evidence from which Grade A recommendations can be made on timing and how to deliver is limited. The current advice is therefore to have discussions with the woman on risks to help her make an informed decision about timing, place, and mode of delivery.

Obesity is an independent risk factor for pregnancy complications including diabetes, hypertension and macrosomia. In those with these complications, the timing of delivery is often influenced by the severity of the complication. As an independent factor, population based observational studies in obese women have shown an increase in the risk of stillbirth. This risk increases linearly with weight from overweight through to class II obesity, but then rises sharply in those with class III obesity by at least 10-fold beyond 42 weeks when compared to normal weight women. This risk of stillbirth is notably higher in obese women from 34 weeks onwards compared to normal weight women. One modifiable risk factor for stillbirth as shown from various cohorts of pregnant women is prolonged pregnancy. Research has linked obesity to prolonged pregnancy. Although the exact mechanism is yet unknown some have linked this to maternal dysregulation of the hypothalamic pituitary adrenal axis leading to hormonal imbalance delaying parturition. For these women the two dilemmas are when and how best to deliver.

In this review, we examine the evidence and make recommendations on the timing and mode of delivery in women with obesity. For class I obese women there are no differences in outcome with regards to timing and mode of delivery when compared to lean weight women. However, for class II and III obesity, planned induction or caesarean sections may be associated with a lower perinatal morbidity and mortality although this may be associated with an increased in maternal morbidity especially in class III obesity. Studies have shown that delivery by 39 weeks is associated with lower perinatal mortality compared to delivering after in these women. On balance the evidence would favour planned delivery (induction or caesarean section) before 40 weeks of gestation. In the morbidly obese, apart from the standard lower transverse skin incision for CS, there is evidence that a supraumbilical transverse incision may reduce morbidity but is less cosmetic. Irrespective of the option adopted, it is important to discuss the pros and cons of each.

A significant body of evidence has supported a negative impact of endometriosis on ovarian follicles; however, the origin and relevance of this ovarian impairment in endometriosis is still a matter of debate. The ovarian damage can be caused by endometriosis itself or by surgeries aiming to remove endometriotic lesions. In this review, we summarized the existing knowledge on the mechanisms by which endometriosis can impact the ovarian follicles, from molecular to clinical points of view. From a molecular standpoint, the presence of endometriosis or its consequences can induce oxidative stress, inflammation, aberrant mitochondrial energy metabolism and inappropriate steroid production in granulosa cells, phenomena that may impair the quality of oocytes to variable degrees. These alterations may have clinical relevance on the accelerated exhaustion of the ovarian reserve, on the ovarian response to gonadotrophin stimulation in IVF cycles and on the competence of the oocytes. Critical points to be considered in current clinical practices related to fertility issues in endometriosis are discussed.

Endometriosis is a complex medical condition with a high prevalence in women of reproductive age. Fertility is compromised in patients with endometriosis, and success in IVF treatments has been a challenge leading to evaluation of different stimulation protocols. The long-standing debate between GnRH agonist long protocols and short GnRH antagonist protocols is being resolved in favor of the latter, since in addition to presenting equivalent results with respect to the traditional option, they have the additional benefit of safety. The good results derived from vitrification techniques have led to the development of new stimulation strategies, such as progestin-primed ovarian stimulation (PPOS), with a greater degree of approval among patients. None of the stimulation protocols currently applied in women with endometriosis has been shown to be superior, so early intervention with an Assisted Reproduction treatment, regardless of the chosen protocol, can provide these women with good chances of motherhood. Women with endometrioma should be counseled for fertility preservation before planned ovarian endometrioma excision. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.