Review

Authors: Xintong Li, Suranga P Kodithuwakku, Rachel W S Chan...

During implantation, a symphony of interaction between the trophoblast originated from the trophectoderm of the implanting blastocyst and the endometrium leads to a successful pregnancy. Defective interaction between the trophoblast and endometrium often results in implantation failure, pregnancy loss, and a number of pregnancy complications. Owing to ethical concerns of using in vivo approaches to study human embryo implantation, various in vitro culture models of endometrium were established in the past decade ranging from two-dimensional cell-based to three-dimensional extracellular matrix (ECM)/tissue-based culture systems. Advanced organoid systems have also been established for recapitulation of different cellular components of the maternal-fetal interface, including the endometrial glandular organoids, trophoblast organoids and blastoids. However, there is no single ideal model to study the whole implantation process leaving more research to be done pursuing the establishment of a comprehensive in vitro model that can recapitulate the biology of trophoblast-endometrium interaction during early pregnancy. This would allow us to have better understanding of the physiological and pathological process of trophoblast-endometrium interaction during implantation.

Topics: Blastocyst; Embryo Implantation; Embryo, Mammalian; Endometrium; Female; Humans; Pregnancy; Trophoblasts

PubMed: 35964080
DOI: 10.1186/s12958-022-00973-8

Review

Authors: A Ohannessian, C Jamin

OBJECTIVE

To establish guidelines of the French National College of Gynecologists and Obstetricians about post-abortion contraception.

MATERIALS AND METHODS

A systematic review of the literature about post-abortion contraception was performed on Medline and Cochrane Database between 1978 and March 2016. The guidelines of the French and foreign scientific societies were also consulted.

RESULTS AND DISCUSSION

After an abortion, if the woman wishes to use a contraception, it should be started as soon as possible because of the very early ovulation resumption. The contraception choice must be done in accordance with the woman's expectations and lifestyle. The contraindications of each contraception must be respected. The long-acting reversible contraception, intra-uterine device (IUD) and implant, could be preferred (grade C) as the efficacy is not dependent on compliance. Thus, they could better prevent repeat abortion (LE3). In case of surgical abortion, IUD should be proposed and inserted immediately after the procedure (grade A), as well as the implant (grade B). In case of medical abortion, the implant can be inserted from the day of mifépristone, the IUD after an ultrasound examination confirming the success of the abortion (no continuing pregnancy or retained sac) (grade C).

Topics: Abortion, Induced; Contraceptive Agents, Female; Drug Implants; Female; Humans; Intrauterine Devices; Pregnancy

PubMed: 27773547
DOI: 10.1016/j.jgyn.2016.09.017

Authors: Thomas M Rawlings, Komal Makwana, Deborah M Taylor...

Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma. We show that acute senescence in glandular epithelium drives secretion of multiple canonical implantation factors, whereas in the stroma it calibrates the emergence of anti-inflammatory decidual cells and pro-inflammatory senescent decidual cells. Pharmacological inhibition of stress responses in pre-decidual cells accelerated decidualization by eliminating the emergence of senescent decidual cells. In co-culture experiments, accelerated decidualization resulted in entrapment of collapsed human blastocysts in a robust, static decidual matrix. By contrast, the presence of senescent decidual cells created a dynamic implantation environment, enabling embryo expansion and attachment, although their persistence led to gradual disintegration of assembloids. Our findings suggest that decidual senescence controls endometrial fate decisions at implantation and highlight how endometrial assembloids may accelerate the discovery of new treatments to prevent reproductive failure.

Topics: Cellular Senescence; Coculture Techniques; Decidua; Embryo Implantation; Endometrium; Female; Humans; Organoids; Pregnancy; Stromal Cells

PubMed: 34487490
DOI: 10.7554/eLife.69603

Randomized Controlled Trial

Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial.

Authors: Nelsilene Carvalho, Deborah Margatho, Kleber Cursino...

OBJECTIVE

To assess the efficacy of an etonogestrel (ENG)-releasing contraceptive implant or the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) in the control of endometriosis-associated pelvic pain.

DESIGN

Noninferiority randomized clinical trial in which women with endometriosis were assigned to use an ENG implant (experimental treatment) or an LNG-IUS (active comparator). Monthly follow-up visits were conducted up to 6 months.

SETTING

University teaching hospital.

PATIENT(S)

One hundred three women, with endometriosis-associated chronic pelvic pain, dysmenorrhea, or both for more than 6 months. In cases of deep endometriosis, vaginal ultrasonography and magnetic resonance imaging were used as additional diagnostic tools.

INTERVENTION(S)

The ENG implant or the LNG-IUS were inserted within the first 5 days of the menstrual cycle.

MAIN OUTCOME MEASURE(S)

Daily scores of noncyclic pelvic pain and dysmenorrhea were evaluated using a daily visual analogue scale. Health-related quality of life was evaluated using the Endometriosis Health Profile-30 questionnaire at baseline and up to 6 months. Bleeding patterns were assessed daily from a menstrual calendar.

RESULT(S)

Both contraceptives improved significantly the mean visual analogue scale endometriosis-associated pelvic pain and dysmenorrhea, without significant differences between treatment group profiles. Health-related quality of life improved significantly in all domains of the core and modular segments of the Endometriosis Health Profile-30 questionnaire, with no difference between both treatment groups. The most common bleeding patterns at 180 days of follow-up were amenorrhea and infrequent bleeding and infrequent bleeding and spotting among ENG implant and LNG-IUS users, respectively.

CONCLUSION(S)

In this noninferiority study both contraceptives improved significantly pelvic pain, dysmenorrhea, and health-related quality of life in endometriosis.

CLINICAL TRIAL REGISTRATION NUMBER

Clinicaltrials.gov under number NCT02480647.

Topics: Adult; Contraceptive Agents, Female; Desogestrel; Drug Implants; Drug Liberation; Endometriosis; Female; Follow-Up Studies; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pain Management; Pelvic Pain

PubMed: 30396557
DOI: 10.1016/j.fertnstert.2018.07.003

Review

Authors: Irene Kwan, Joseph Loze Onwude

INTRODUCTION

A woman has premenstrual syndrome (PMS) if she complains of recurrent psychological and/or physical symptoms occurring during the luteal phase of the menstrual cycle, and often resolving by the end of menstruation. Symptom severity can vary between women. Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms occur in about 5% of those women. There is no consensus on how symptom severity should be assessed for PMS, which has led to the use of a wide variety of symptom scores and scales, thus making it difficult to synthesise data on treatment efficacy. The cyclical nature of the condition also makes it difficult to conduct RCTs.

METHODS AND OUTCOMES

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of continuous hormonal treatments in women with premenstrual syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

RESULTS

At this update, searching of electronic databases retrieved 132 studies. After deduplication and removal of conference abstracts, 132 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 102 studies and the further review of 30 full publications. Of the 30 full articles evaluated, one systematic review and three RCTs were added to this overview. We performed a GRADE evaluation for three PICO combinations.

CONCLUSIONS

In this systematic overview, we categorised the efficacy for three interventions based on information relating to the effectiveness and safety of continuous combined oral contraceptives, continuous transdermal estradiol, and continuous subcutaneous estradiol implants.

Topics: Administration, Cutaneous; Contraceptives, Oral, Combined; Drug Implants; Estradiol; Female; Humans; Infusions, Subcutaneous; Premenstrual Syndrome

PubMed: 26303988
DOI: No ID Found

Authors: Laura Vang Sparsø, Christina Laamanen Sommer, Arne Hørlyck...

This case report details a rare case of contraceptive implant migration in a young woman. The migration was discovered three years post-insertion during a routine replacement visit. Despite the absence of pulmonary symptoms, a CT scan revealed the implant in the inferior lobe of the right lung. The patient was referred for further evaluation, but immediate surgical removal was deferred. This case report highlights the importance of healthcare providers recognising migration as a rare complication during implantation and suggests self-examination as a potential preventive strategy.

Topics: Humans; Female; Foreign-Body Migration; Drug Implants; Contraceptive Agents, Female; Tomography, X-Ray Computed; Lung; Adult; Desogestrel

PubMed: 39115213
DOI: 10.61409/V03240203

Review

Authors: Ravi Vaishya, Varun Khurana, Sulabh Patel...

INTRODUCTION

Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations.

AREAS COVERED

This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics.

EXPERT OPINION

Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

Topics: Biological Products; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Drug Implants; Drug Liberation; Drug Stability; Gels; Hydrogen-Ion Concentration; Microspheres; Nanoparticles; Peptides; Polymers; Proteins

PubMed: 25251334
DOI: 10.1517/17425247.2015.961420

Authors: Si-Ting Chen, Feng Ran, Wen-Wen Shi...

INTRODUCTION

Nutritional deficiency occurs frequently during pregnancy and breastfeeding. Tryptophan (Trp), an essential amino acid which is critical for protein synthesis, serves as the precursor for serotonin, melatonin, and kynurenine (Kyn). The imbalance between serotonin and kynurenine pathways in Trp metabolism is closely related to inflammation and depression. This study assessed the effects of Trp deficiency on mouse early pregnancy.

METHODS

Embryo implantation and decidualization were analyzed after female mice had been fed diets containing 0.2% Trp (for the control group), 0.062% Trp (for the low Trp group) and 0% Trp (for the Trp-free group) for two months. The uteri of the mice were collected on days 4, 5, and 8 of pregnancy for further analysis.

RESULTS

On day 8 of pregnancy, the number of implantation sites were found to be similar between the control and the low Trp groups. However, no implantation sites were detected in the Trp-free group. On day 5 of pregnancy, plane polarity- and decidualization-related molecules showed abnormal expression pattern in the Trp-free group. On day 4 of pregnancy, there was no significant difference in uterine receptivity molecules between the low-Trp group and the control group, but uterine receptivity was abnormal in the Trp-free group. At implantation sites of the Trp-free group, IDO and AHR levels were markedly elevated. This potentially increased levels of Kyn, 2-hydroxy estradiol, and 4-hydroxy estradiol to affect decidualization.

CONCLUSIONS

Trp-free diet may impair decidualization via the IDO-KYN-AHR pathway.

Topics: Animals; Female; Embryo Implantation; Tryptophan; Mice; Pregnancy; Decidua; Diet; Kynurenine

PubMed: 38752181
DOI: 10.3389/fendo.2024.1356914

Review

Authors: Nava Dekel, Yulia Gnainsky, Irit Granot...

Approximately half of all human embryo implantations result in failed pregnancy. Multiple factors may contribute to this failure, including genetic or metabolic abnormalities of the embryo. However, many of these spontaneous early abortion cases are attributed to poor uterine receptivity. Furthermore, although many fertility disorders have been overcome by a variety of assisted reproductive techniques, implantation remains the rate-limiting step for the success of the in vitro fertilization (IVF) treatments. It has been demonstrated that endometrial biopsies performed either during the spontaneous, preceding cycle, or during the IVF cycle itself, significantly improve the rate of implantation, clinical pregnancies and live births. These observations suggest that mechanical injury of the endometrium may enhance uterine receptivity by provoking the immune system to generate an inflammatory reaction. In strong support of this idea, we recently found that dendritic cells (DCs), an important cellular component of the innate immune system, play a critical role in successful implantation in a mouse model. In this review, we discuss the hypothesis that the injury-derived inflammation in the biopsy-treated patients generates a focus for uterine DCs accumulation that, in turn, enhances the endometrial expression of essential molecules, which facilitate the interaction between the embryo and the uterine epithelium.

Topics: Embryo Implantation; Female; Humans; Inflammation; Pregnancy; Reproductive Techniques, Assisted

PubMed: 20059465
DOI: 10.1111/j.1600-0897.2009.00792.x

Randomized Controlled Trial

Authors: Jason Bacharach, Andrew Tatham, Gloria Ferguson...

OBJECTIVE

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

METHODS

This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).

RESULTS

Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2-7.4, 6.5-7.8, and 6.1-6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group.

CONCLUSIONS

The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. CLINICALTRIALS.

GOV IDENTIFIER

NCT02250651.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Dose-Response Relationship, Drug; Double-Blind Method; Drug Implants; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Timolol; Young Adult

PubMed: 34724172
DOI: 10.1007/s40265-021-01624-9