ELIRAN MOR

 Authors must include a statement that consent has been obtained from each patient after full explanation of the purpose and nature of all procedures used. For research requiring ethics committee approval, please include a statement to this effect in the manuscript. Also indicate whether patient consent was obtained in line with the below policy. We will be unable to accept research papers without this statement.

 Where possible, identifying information, including names, initials, or hospital numbers, should not be published in written descriptions, photographs, or pedigrees unless the information is essential for scientific purposes and the patient (or parent or guardian) gives written informed consent for publication. Any identifiable patient must be shown the manuscript to be published before being asked to give consent. Authors should disclose to these patients whether any potential identifiable material might be available online or in print after publication. Informed consent should be obtained if there is any doubt that anonymity can be maintained. We no longer publish pictures with black bands across the eyes without a signed consent form, because bands fail to mask someone’s identity effectively.

 The patient (or parent or guardian) must give written informed consent for publication by signing our consent form. Signed consent forms should then be retained in the patient's clinical notes for future reference, and a copy should be made available for review by the Editor on request.

 The manuscript reporting this patient's details should state that 'Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient/parent/guardian/ relative of the patient'. If the patient is deceased the authors should seek permission from a relative and include a statement to this fact. If neither the patient or a relative can be traced, we can only publish if we are satisfied the information has been sufficiently anonymised, making it impossible to identify the patient with any certainty.

 Permission is not required to publish the 'recordings' listed below, provided that, the recordings are effectively anonymised by the removal of any identifying marks, and patient details (i.e. patient name, date of birth, name of hospital) from images before submission:

 Articles will only be considered if the procedures used are clearly described and conformed with the international and national legal and ethical requirements, as well as the requirements outlined by the institution in which the work took place. A statement identifying the committee approving the study must also be included in the Methods section.

 Editors reserve the right to request further information on the exact procedures and ethical approval obtained as part of the review process. Papers may be rejected on ethical grounds should the editors feel the study does not adequately meet current international guidelines for humane research.

 In general, studies that are based on observations performed in a single cell line will not be considered for publication if other lines of the same general lineage and characteristics are available. If at all possible, observations should be replicated in multiple cell lines.

 No specific feature within an image may be enhanced, obscured, moved, removed or introduced. The groupings of images from different parts of the same gel, or from different gels, fields or exposures must be made explicit by the arrangement of the figure (eg using dividing lines) and in the text of the figure legend.

 Adjustments of brightness, contrast or colour balance are acceptable if and as long as they do not obscure or eliminate any information present in the original. Nonlinear adjustments (eg changes to gamma settings) must be disclosed in the figure legend. Adjustments should be applied to the entire image.

 It is the author’s responsibility to document that the results are reproducible and that the differences found are not due to random variation. No absolute rules can be applied but, in general, quantitative data should be from no fewer than three replicate experiments. Appropriate statistical methods should be used to test the significance of differences in results. The term ‘significant’ should not be used unless statistical analysis was performed, and the probability value used to identify significance (eg P < 0.05) should be specified.

 When several t-tests are employed, authors should be aware that nominal probability levels no longer apply. Accordingly, the multiple t-test, multiple range test or similar techniques to permit simultaneous comparisons should be employed. Also, in lieu of using several t-tests, it is often more appropriate to utilize an analysis of variance (ANOVA) to permit pooling of data, increase the number of degrees of freedom, and improve reliability of results. Authors should use appropriate nonparametric tests when the data depart substantially from a normal distribution.

 Bar charts are discouraged; scatter plots more faithfully describe the data being presented. When data points are fitted with lines, specify the method used for fitting (graphical, least squares, computer program). If differences in slopes and/or axis intercepts are claimed for plotted lines, these should be supported by statistical analysis.

 Authors are strongly encouraged to deposit data sets in appropriate public databases, such as GenBank or Gene Expression Omnibus (GEO). Authors should include the relevant database identifiers and accession numbers for deposited sequences within the manuscript using the following format: Database: xxxx, eg: GEO: GSE6364. Authors are also required to provide the URL for the sequence(s).

 During the submission process the submitting author will need to complete a publication agreement on behalf of the co-authors and the copyright holder for the article. As part of this agreement, the copyright holder will grant the Society for Reproduction and Fertility and Bioscientifica a non-exclusive licence to publish the article. The copyright is retained by the original copyright holder and is not assigned to Society for Reproduction and Fertility or Bioscientifica.

 Authors are entitled to appeal against a rejection decision made by a journal. Appeals should be submitted to the journal email address. We must receive your valid appeal within four weeks of the original decision, otherwise it will not be considered. An appeal is considered to be an extension of the peer review process and so you should not submit your article to another publication whilst an appeal is ongoing.

 To be considered, appeals must directly address the reason(s) given for the initial rejection decision. If reviewer reports were included with the decision letter, then these criticisms must be responded to in the appeal, however you should not prepare and submit a revised version of your article with the appeal. Appeals that are received late, do not address reviewers’ criticisms, are dismissive of the reviewer comments, or contain offensive language will not be considered.

 If successful, an appeal may result in the decision being rescinded and a continuation of the peer-review process. If the appeal is rejected, then the original rejection decision is upheld and no further consideration of that article is possible.

 This Committee Opinion was developed jointly by the American College of Obstetricians and Gynecologists' Committee on Gynecologic Practice and the American Society for Reproductive Medicine in collaboration with committee member Daniel M. Breitkopf, MD and ASRM member Micah Hill, DO.

Dr Eliran

 ABSTRACT: The goal of prepregnancy care is to reduce the risk of adverse health effects for the woman, fetus, and neonate by working with the woman to optimize health, address modifiable risk factors, and provide education about healthy pregnancy. All those planning to initiate a pregnancy should be counseled, including heterosexual, lesbian, gay, bisexual, transgender, queer, intersex, asexual, and gender nonconforming individuals. Counseling can begin with the following question: “ Would you like to become pregnant in the next year ?” Prepregnancy counseling is appropriate whether the reproductive-aged patient is currently using contraception or planning pregnancy. Because health status and risk factors can change over time, prepregnancy counseling should occur several times during a woman's reproductive lifespan, increasing her opportunity for education and potentially maximizing her reproductive and pregnancy outcomes. Many chronic medical conditions such as diabetes, hypertension, psychiatric illness, and thyroid disease have implications for pregnancy outcomes and should be optimally managed before pregnancy. Counseling patients about optimal intervals between pregnancies may be helpful to reduce future complications. Assessment of the need for sexually transmitted infection screening should be performed at the time of prepregnancy counseling. Women who present for prepregnancy counseling should be offered screening for the same genetic conditions as recommended for pregnant women. All patients should be routinely asked about their use of alcohol, nicotine products, and drugs, including prescription opioids and other medications used for nonmedical reasons. Screening for intimate partner violence should occur during prepregnancy counseling. Female prepregnancy folic acid supplementation should be encouraged to reduce the risk of neural tube defects.

 Any patient encounter with nonpregnant women or men with reproductive potential (eg, not posthysterectomy or poststerilization) is an opportunity to counsel about wellness and healthy habits, which may improve reproductive and obstetric outcomes should they choose to reproduce.

 The goal of prepregnancy care is to reduce the risk of adverse health effects for the woman, fetus, and neonate by working with the woman to optimize health, address modifiable risk factors, and provide education about healthy pregnancy.

 Women should be counseled to seek medical care before attempting to become pregnant or as soon as they believe they are pregnant to aid in correct dating and to be monitored for any medical conditions in which treatment should be modified during pregnancy.

 Obstetrician–gynecologists have a prime opportunity to improve maternal and fetal outcomes through prepregnancy counseling. Like a well-woman visit, the prepregnancy visit (when the patient presents to discuss a potential future pregnancy) provides an excellent opportunity to counsel patients about maintaining a healthy lifestyle and minimizing health risks 1. The goal of prepregnancy care is to reduce the risk of adverse health effects for the woman, fetus, and neonate by working with the woman to optimize health, address modifiable risk factors, and provide education about healthy pregnancy. Prepregnancy counseling should include a review of a patient's immunizations, an assessment for immunity, and other screenings and tests, as appropriate. All those planning to initiate a pregnancy should be counseled, including heterosexual, lesbian, gay, bisexual, transgender, queer, intersex, asexual, and gender nonconforming individuals. Pregnancy complications may be reduced by appropriate identification and mitigation of risk factors, while genetic screening may allow a couple to make informed decisions regarding family planning. Management of preexisting medical conditions may be optimized during the prepregnancy period, reducing the chances of pregnancy-related complications. Additionally, understanding aspects of patients' social context during prepregnancy counseling may identify ways to help improve prenatal care usage, including understanding barriers that patients may face when accessing health care.

 Direct screening for a patient's pregnancy intentions, as stated in the “One Key Question Initiative,” is a core component of high-quality, primary preventive care services 2. Any patient encounter with nonpregnant women or men with reproductive potential (eg, not posthysterectomy or poststerilization) is an opportunity to counsel about wellness and healthy habits, which may improve reproductive and obstetric outcomes should they choose to reproduce. Counseling can begin with the following question: “ Would you like to become pregnant in the next year ?” Prepregnancy counseling is appropriate whether the reproductive-aged patient is currently using contraception or planning pregnancy. Because health status and risk factors can change over time, prepregnancy counseling should occur several times during a woman's reproductive lifespan, increasing her opportunity for education and potentially maximizing her reproductive and pregnancy outcomes. Additionally, prepregnancy counseling can be performed by the obstetrician–gynecologist of an infertile patient before referral to a reproductive endocrinologist, further streamlining patient education. The American College of Obstetricians and Gynecologists and ASRM support coverage for and access to recommended prepregnancy counseling and services as a core component of women's health care.

 Family planning is a foundational aspect of prepregnancy counseling. Approximately 45% of the pregnancies in the United States are unintended, and unintended pregnancy increases the risk of pregnancy complications 3. Education and enhanced awareness of the effect of age on fertility 4 and planning for family size are essential in counseling the patient who desires pregnancy. Counseling patients about optimal intervals between pregnancies may be helpful to reduce future complications. Women should be advised to avoid interpregnancy intervals shorter than 6 months and should be counseled about the risks and benefits of repeat pregnancy sooner than 18 months 5 6. Short interpregnancy intervals also are associated with reduced vaginal birth after cesarean success for women undergoing labor after cesarean (also referred to as trial of labor after cesarean) 7. The Centers for Disease Control and Prevention's (CDC) U.S. Medical Eligibility Criteria for Contraceptive Use and U.S. Selected Practice Recommendations for Contraceptive Use 8 9 can be used to facilitate evidence-based contraception counseling to meet an individual patient's family planning and pregnancy spacing needs. For infertile women planning to use assisted reproductive technology to become pregnant, a pregnancy interval less than 18 months but greater than 6 months may be advisable 10.

 An ovulatory woman who is younger than 35 years who desires pregnancy and who does not have a clearly identifiable risk factor for infertility should be expeditiously evaluated if she has not become pregnant after 12 months of unprotected intercourse. A woman who is 36 years and older should be evaluated after 6 months. A comprehensive evaluation should be conducted and treatment initiated by a heath care provider with adequate training and expertise. For anovulatory women and those with a clearly identifiable risk factor for infertility, strong consideration should be given to evaluation and treatment upon presentation.

 Referral to a fertility specialist for males and females may be considered at any point if the infertility etiology, indicated treatment, or attempted treatment failures exceeds the expertise of the obstetrician–gynecologist. Monthly ovulation is likely in women with regular and predictable menses with no greater than 2–3-day variance within a range of 25–35 days. For example, a woman with cycles every 26–28 days is likely ovulatory, while a woman with cycles of 25, 34, 26, then 35 days is likely not ovulatory. Patients desiring pregnancy should be counseled that the fertile window is having sexual intercourse in the 3–4 days before ovulation and that intercourse every 1–2 days yields the highest pregnancy rates 11. Patients may inquire about ovulation predictor kits or electronic apps for fertility. These tools vary in quality, and data on their usefulness are limited 12.

 Many chronic medical conditions such as diabetes, hypertension, psychiatric illness, and thyroid disease have implications for pregnancy outcomes and should be optimally managed before pregnancy Table 1. Consideration may be given to referral to a maternal–fetal medicine specialist. Data are insufficient to recommend for or against universal screening for subclinical thyroid disease; however, screening may be appropriate for patients with risk factors (eg, age greater than 30 years, morbid obesity, history of pregnancy loss, preterm delivery, or infertility) 13.

 All prescription and nonprescription medications should be reviewed during prepregnancy counseling. This review also should include nutritional supplements and herbal products that patients may not consider to be medication use but could affect reproduction and pregnancy. The pregnancy safety of each medication and supplement should be discussed. Medications with potential teratogenicity should be reviewed and the specific risks of each individual medication discussed in detail. The importance of reliable contraception should be emphasized when a patient is taking potentially teratogenic medications. For a patient who desires pregnancy, potentially teratogenic medication should be adjusted in collaboration with the prescribing health care provider before the patient discontinues contraception. The lowest effective doses of the safest medications should be used whenever it is medically reasonable to do so. For information on the effects of medications used to manage depression during pregnancy, see The Management of Depression During Pregnancy , a report jointly developed by ACOG and the American Psychiatric Association 14. Male partners should be screened for the use of androgens, such as testosterone. Androgen use is associated with azoospermia and infertility in males, which may be reversible in some cases with cessation 15 16.

 A genetic and family history of the patient and her partner should be obtained 17 18 19 20. This may include family history of genetic disorders, birth defects, mental disorders, and breast, ovarian, uterine, and colon cancer. When any genetic disease carrier status is diagnosed in one or both partners, full medical records review and genetic counseling are recommended to educate the patient on the effects of the disease and the potential options for prepregnancy and early pregnancy screening of offspring. Women who present for prepregnancy counseling should be offered screening for the same genetic conditions as recommended for pregnant women, though insurance coverage for screening may be lacking and may be a barrier for some patients. Screening in the prepregnancy period offers the additional advantages of identifying, before pregnancy, couples at risk of having children with genetic diseases and offering appropriate testing to optimize patient education, counseling, and options for achieving pregnancy. Couples at risk of having children with specific genetic diseases can be counseled about the disease inheritance and course and offered referral for potential interventions, such as preimplantation genetic testing. See Table 2 for counseling and screening recommendations.

 Women of reproductive age should have their immunization status assessed annually for Tdap, measles–mumps–rubella, hepatitis B, and varicella. All patients should receive an annual influenza vaccination; those women who are or will be pregnant during influenza season will have additional benefits 21. Adult women who have never received a dose of Tdap or whose Tdap vaccination status is unknown should receive a single dose, as recommended for nonpregnant adults by the CDC. Additionally, Tdap vaccine should be given to all women during each pregnancy between 27–36 weeks regardless of prepregnancy immunization history. Human papillomavirus vaccination (HPV) and cervical cancer screening should be performed in accordance with current guidelines. The HPV vaccination currently is not recommended during pregnancy but should not be avoided or delayed because a woman may want to become pregnant or may be actively trying to become pregnant. If the HPV vaccine series is started and a patient then becomes pregnant, completion of the vaccine series should be delayed until that pregnancy is completed 22 23. Vaccinations for rubella and varicella should be given at least 28 days before pregnancy, or in the postpartum period if not previously given. Because two doses of the varicella vaccine are recommended, and the CDC recommends that women not become pregnant for 1 month after being vaccinated, a woman who desires pregnancy should begin vaccination 2 months before attempting pregnancy 24. Some advanced-reproductive-age patients may wish to reproduce, and those age 50 years and older should also be vaccinated against herpes zoster 25. The need for other immunizations should be assessed during a prepregnancy visit by reviewing health, lifestyle, and occupational risks of other infections and administering required doses as indicated 26. The CDC's Advisory Committee on Immunization Practice immunization schedules provide the most current information on immunization recommendations 27.

 Assessment of the need for STI screening should be performed at the time of prepregnancy counseling. Guidance on recommended STI screening is available from the CDC 28 and ASRM 29. Gonorrhea, chlamydial infection, syphilis, and human immunodeficiency virus (HIV) should be screened for based on age and risk factors. Counseling to reduce STI risk should be provided 26. For current guidance on hepatitis C screening for nonpregnant women, see the CDC's recommendations 30. Those at high risk of tuberculosis should be screened and treated appropriately before pregnancy 26. Exposure to toxoplasmosis should be assessed and avoidance counseled. Much attention has been given to educational programs to reduce maternal Toxoplasma gondii infection and, thus, congenital toxoplasmosis. However, despite the successes demonstrated in some observational studies, several reviews (including a Cochrane review) suggest that weaknesses in study design prevent the conclusion that such strategies effectively reduce congenital toxoplasmosis 31. Patients with potential exposure to certain infectious diseases, such as the Zika virus, should be counseled regarding travel restrictions and appropriate waiting time before attempting pregnancy. Obstetrician–gynecologists may ask the patient about recent or upcoming travel history for herself and her partner. The CDC offers up-to-date guidance on Zika precautions 32 and other infectious diseases 33. Information and guidance on the Zika virus also is available from ACOG 34 and ASRM 35.

 All reproductive-aged patients living with HIV should receive prepregnancy counseling if considering pregnancy 36. Prepregnancy counseling should include a detailed discussion of interventions to reduce the risk of perinatal transmission, ways to optimize long-term health, and the possible effects of antiretroviral medications on the fetus. Any HIV-infected patients who are contemplating pregnancy should be counseled that they should be receiving treatment with antiretroviral therapy, with the goal of a plasma viral load suppressed to an undetectable level before achieving pregnancy. Artificial insemination is the safest way for an HIV-infected couple to become pregnant while minimizing the risk of HIV transmission to an HIV-negative partner 37. Prepregnancy administration of antiretroviral preexposure prophylaxis for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission 38. A non-HIV-infected woman with an HIV-infected male partner with whom she wants to achieve pregnancy should be offered a referral to a subspecialist with the requisite training and experience in infectious disease or reproductive endocrinology and infertility for counseling. Like prepregnancy counseling for non-HIV-infected women, the goals for HIV-infected women are to improve the health of the women before pregnancy and to identify risk factors for adverse maternal and fetal outcomes. Safe sex practices and avoidance of STIs should be discussed, and both partners should be screened for STIs, which should be treated if present. The choice of antiretroviral therapy in women of childbearing capacity should take into consideration the regimen's effectiveness, the women's hepatitis B status, the teratogenic potential of the medications, potential drug interactions, and possible maternal and fetal adverse outcomes 37. See ACOG's Practice Bulletin No. 167, Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus , for more information.

 All patients should be routinely asked about their use of alcohol, nicotine products, and drugs, including prescription opioids and other medications used for nonmedical reasons 39 40. Adverse effects associated with smoking during pregnancy include intrauterine growth restriction, placenta previa, abruptio placentae, decreased maternal thyroid function 41 42, preterm prelabor rupture of membranes (also referred to as premature rupture of membranes) 43 44, low birth weight, perinatal mortality 41, and ectopic pregnancy 41. Children born to women who smoke during pregnancy are at an increased risk of asthma, infantile colic, and childhood obesity 45 46 47. Pregnancy appears to motivate women to stop smoking; 46% of prepregnancy smokers quit smoking directly before or during pregnancy 48; however, women who are unable to quit during pregnancy likely have a tobacco use disorder 49. Effective strategies for tobacco cessation should be employed, such as the 5A's intervention model 40.