Case presentation: infertility and subfertility

Case presentation: a pregnant woman with infertilityKeli ChowClinical scenarioMs FC is an obese 41 year old primigravida who comes in for an antenatal check up at 9 weeks gestation. She has a 4 year history of primary infertility and this current pregnancy was conceived by IVF. She has come in with her partner.Past Medical Hx4 year hx of primary infertilityEndometriosis in 2010, cleared by D&C in 2012Long term hypertension on methyldopa 250mgDepression on imipramine hydrochloride Hypothyroidism taking thyroxineFamily HxSister has had gestational diabetes in previous pregnancyFather has haemochromatosis FC does not know if she is a carrierDepressionMedicationsMethyldopa 250mgImipramine hydrochloride 60mg daily since 2002. Reduced from 150m 12mths ago (teratogenic).NKDANil smoking, alcohol or recreational drug useSocial HxLives at home with husband, good social supportOccupation as lecturer at university driving may become a problem in later pregnancy with obesityAntenatallyG1P0Blood group O+veConfirmed 9 weeks pregnant, LMP 10/01/2014; EDD: 15/10/2014Conceived with donor egg of age 23Paps up to date, NAD (unknown date of last)Fe levels normalNo significant fhx of leukaemia, chromosomal abnormalities on either sideAntenatallyS/S of pregnancyNo symptoms of HTN or diabetes so farNo vaginal bleeding or dischargeSlight nausea but no vomitingNo fever or illness reportedExamination 170cm, 117.3kg, BMI is 40.6BP 130/80 (well controlled)Pulse 93

InvestigationsUltrasound at 6 weeks was normalGestational sac 17.4mm meanCRL 7.8mmFetal heart rate present 114bpm freq

Blood tests all relatively normalHb 15.6g/L,HCT 0.48(H),MCV 96,Platelets 140x109L, TSH 1.16mU/L,free T4 14.0pmol/L,VitD 71All vaccinations performed, no HIV/HepPoints of interestFC is 41, however egg donor is only 23 meaning risk of chromosomal abnormalities is significantly reduced. Preexisting hypertension preeclampsiaSister had gestational diabetesDepression risk of postnatal depression, drugs are teratogenic?Haemachromatosis is she or her husband carriers?Obesity problems with delivery, labour, antenatal carePlanConsider 12 week ultrasound.FC decides she would not likely terminate pregnancy even if positive test, so no point doing combined first trimester screening test. Instead, she will wait for the 20 week US.Infertility (subfertility)Definition varies; WHO states it is the inability to conceive a child. No pregnancy after 2 years of regular sexual intercourse. Also includes inability to maintain pregnancy or carry a pregnancy to live birth.Primary infertility: no previous child, secondary infertility: failure to conceive following previous pregnancyFactors to consider>3 years of tryingLow coital frequencyInappropriate timing (not at ovulation)No previous pregnancyBMI 30Counsel first, and investigations undertaken after 1 year of unprotected intercourse, but only 6 months if >35 years of age.Causes of female subfertilityOvulation problemsE.g. GnRH disruption like stress, weight change, structural lesions/tumours, systemic diseases -> anovulation and amenorrhoea.Most common cause is PCOS. Others include premature ovarian failure, viruses/toxins, pelvic surgery, irradiation, chemotherapy, autoimmune problemsCauses of female subfertilityTubal dysfunctionPelvic infection, endometriosis, pelvic surgery, STIs (chlamydia)Disorders of placentationDefects in endometrial development, submucous fibroidsCauses of male subfertilityDisorders of spermatogenesis (impairment)Undescended testis, varicocele, tight underwear, chromosomal abnormalities (Y chromosome microdeletions).Psychotropic drugs, antiepileptic medication, some antibiotics, chemotherapeutic agentsDisorders of sperm transportCongenital malformations, inflammation, infectionEjaculatory problemsDrugs, idiopathic, diabetes, MSInitial managementExamine both partnersAdvise to stop smoking and lose weight, and take folic acid 0.4mg/dayAsk female about menstrual hx, previous pregnancies, contraception, previous infections or surgery, drugsAsk male: puberty, surgery, illnesses, drugs, alcohol, job (home at ovulation), erectile problemsExaminationExamination of both partners needed. Including BMIMales: assess testicular size, masses, congenital absence of vas deferens and varicocele. Small testes may be associated with primary testicular failure.Women: full general and pelvic exam.

InvestigationsHPO axis: LH, FSH for ovarian reserve, mid-luteal progesterone to confirm ovulation, endocrine abnormalities (hypothyroid, hyperprolactinaemia and androgen levels)Semen analysisAssessment of tubal patencyHysterosalpingogramUltrasonography with contrastLaparoscopy (methylene blue)Treatment of subfertilityOvulation problemsLifestyle changesOvulation induction by clomid or exogenous gonadotrophin (hCG binds to LH receptor)If PCOS: metformin or ovarian drillingHyperprolactinaemia needs full investigationRx: dopaminergic agonist or surgery

Treatment of subfertilityTubal diseaseIVFLaparoscopic adhesiolysisFimbrioplasty if fibriae has adhesionsMale subfertilityExogenous gonadotrophins for hypogonadotrophic hypogonadismArtificial insemination with ovarian stimulationIVF +/- ICSIDonor spermAssisted conceptionIVFUsually used for tubal problemsPituitary downregulated, ovaries stimulated, ova collected, fertilized, 2 embryos returned under US guidance to uterusIntracytoplasmic sperm injection (ICSI) - direct injection of sperm into egg, for severe male subfertilityIntrauterine insemination (IUI)Sperm placed into uterus during ovulationFor mild male subfertilityDonor inseminationIf risk of genetic disorder via male partner or single womenDonor eggsGenetic conditions e.g. Fragile X, Turners syndrome, ovarian failure

Risks of assisted conceptionOvarian hyperstimulation syndromeResponse to exogenous gonadotrophins/analogues for superovulation.Causes abdominal pain, distension, nausea, SOB, poor urinary outputEctopic pregnancyEmbryo may migrate there or be placed there during embryo transfer procedureMultiple pregnancy24ReferencesMonga A, editor. Gynaecology by ten teachers. 18th ed. New York: Edward Arnold; 2006.Collier J. Oxford Handbook of clinical specialties. 9th ed. New York: Oxford; 2013. p. 292-5.World Health Organization. Infertility [Internet]. Geneva: WHO; 2014 [cited 2014 Apr 31]. Available from: http://www.who.int/topics/infertility/en/ Miller K. Intracytoplasmic sperm injection. In: UpToDate [cited 2014 Apr 31]. Available from: http://www.uptodate.com/contents/intracytoplasmic-sperm-injectionMarion, DW. Diaphragmatic pacing. In: UpToDate, Post TW (Ed), UpToDate,Waltham, MA. (Accessed on November 25, 2013.)25